Charles Hardin Holley was born on September 7, 1936, in Lubbock, Texas, to Lawrence Odell and Ella Pauline (Drake) Holley. In Philip Norman's biography, it is stated that his mother's family claimed to be descended from the English navigator Francis Drake.

Holly was always called "Buddy" by his family. Buddy was the youngest of three siblings, and brothers Larry and Travis taught him to play a variety of instruments, including the guitar, four-string banjo and lap steel guitar. At the age of five, his young voice and exuberance won him a talent contest singing a then-popular song, "Have You Ever Gone Sailing (Down the River of Memories)." In 1949, while still retaining his youthful soprano voice, he recorded a bluesy solo rendering of Hank Snow's "My Two Timin' Woman" on a wire recorder borrowed by a friend who worked in a music shop.

In 1952, he met Bob Montgomery at Hutchinson Junior High School. They shared an interest in music, and teamed up as "Buddy and Bob". Initially influenced by bluegrass, they sang harmony duets at local clubs and high school talent shows. The duo performed on a local radio station KDAV Sunday broadcast that made them a top local act. Hutchinson Junior High School now has a mural honoring Holly, and Lubbock High School, where he sang in the school choir, also honors the late musician.

Holly saw Elvis Presley sing in Lubbock in 1955, and began to incorporate a rockabilly style, similar to the Sun Records sound, which had a strong rhythm acoustic and slap bass. On October 15, 1955, Holly, along with Bob Montgomery and Larry Welborn, opened the bill for Presley in Lubbock, catching the eye of a Nashville talent scout. Holly's transition to rock continued when he opened for Bill Haley & His Comets at a local show organized by Eddie Crandall, the manager for Marty Robbins.

Following this performance, Decca Records signed him to a contract in February 1956, misspelling his name as "Holly". He thereafter adopted the misspelled name for his professional career. Holly formed his own band, later to be called The Crickets, consisting of Holly (lead guitar and vocals), Niki Sullivan (guitar), Joe B. Mauldin (bass), and Jerry Allison (drums). They went to Nashville for three recording sessions with producer Owen Bradley. However, Holly chafed under a restrictive atmosphere that allowed him little input. Among the tracks he recorded was an early version of "That'll Be The Day", which took its title from a line that John Wayne's character says repeatedly in the 1956 film The Searchers. (This initial version of the song played more slowly and about half an octave higher than the later hit version.) Decca released two singles, "Blue Days, Black Nights" and "Modern Don Juan", that failed to make an impression. On January 22, 1957, Decca informed Holly his contract would not be renewed, insisting, however, that he could not record the same songs for anyone else for five years.

Holly then hired Norman Petty as manager, and the band began recording at Petty's studios in Clovis, New Mexico. Petty contacted music publishers and labels, and Brunswick Records, a subsidiary of Decca, signed the Crickets on March 19, 1957. Holly signed as a solo artist with another Decca subsidiary, Coral Records. This put him in the unusual position of having two recording contracts at the same time.

On May 27, 1957, "That'll Be The Day" was released as a single, credited to the Crickets to try to bypass Decca's claimed legal rights. When the song became a hit, Decca decided not to press its claim. "That'll Be the Day" topped the Billboard US "Best Sellers in Stores" chart on September 23, and was No. 1 on the UK Singles Chart for three weeks in November. The Crickets performed "That'll Be the Day" and "Peggy Sue" on The Ed Sullivan Show on December 1. They also sang "Peggy Sue" on The Arthur Murray Party on December 29 and were given a polite introduction by Kathryn Murray. The kinescopes of these programs are the only record of their 1957 television appearances.

Holly helped win over an all-black audience to rock and roll/rockabilly when the Crickets were booked at New York's Apollo Theater for August 16–22, 1957. Unlike the immediate acceptance shown in the 1978 movie The Buddy Holly Story, it actually took several performances for the audience to warm up to him. In August 1957, the Crickets were the only white performers on a national tour including black neighborhood theaters.

As Holly was signed both as a solo artist and a member of the Crickets, two debut albums were released: The "Chirping" Crickets on November 27, 1957 and Buddy Holly on February 20, 1958. His singles "Peggy Sue" and "Oh Boy!", with backing vocals later dubbed on by The Picks, reached the top ten of United States and United Kingdom charts. Buddy Holly and the Crickets toured Australia in January 1958 and the UK in March. Their third and final album, That'll Be the Day, was put together from early recordings and was released in April.

In the liner notes to Buddy Holly: The Definitive Collection, Billy Altman notes that "Peggy Sue" was originally written as "Cindy Lou" (after Holly's niece), but Holly changed it prior to recording as a tip of the hat to Crickets drummer Jerry Allison's girlfriend, Peggy Sue Gerron. Allison wanted the song to be named after Gerron to make up for a recent fight. The two later married.

Holly wrote "True Love Ways" about his relationship with his wife, Maria Elena. It was recorded in her presence on October 21, 1958, at Decca's Pythian Temple, with Dick Jacob, Coral-Brunswick's new head of Artists and Repertoire, serving as both producer and conductor of the 18-piece orchestra, which included members of the New York Symphony Orchestra, NBC Television's house orchestra and Abraham "Boomie" Richman, formerly of Benny Goodman's band.

In June 1958, he met Maria Elena Santiago, a receptionist for Murray Deutch, an executive for New York publisher Peer-Southern Music. Holly managed to have Santiago invited to a luncheon at Howard Johnson's, thanks to Deutch's secretary, Jo Harper. He asked her to have dinner with him that night at P. J. Clarke's. Holly proposed marriage to her on their very first date. "While we were having dinner, he got up and came back with his hands behind his back. He brought out a red rose and said, 'This is for you. Would you marry me?' Within the beautiful red rose, there was a ring. I melted." Holly went to her guardian's house the next morning and Maria came running at him and jumped into his arms, which was a sign to him that it was a "yes".

They married in Lubbock on August 15, 1958, less than two months later. "I'd never had a boyfriend in my life. I'd never been on a date before. But when I saw Buddy, it was like magic. We had something special: love at first sight. It was like we were made for each other. He came into my life when I needed him, and I came into his," she told the Lubbock Avalanche-Journal on what would have been their 50th wedding anniversary. The newlyweds honeymooned in Acapulco. Maria Elena traveled on tours, doing everything from the laundry to equipment setup to ensuring the group got paid. However, many fans became aware of his marriage only after his death.

The ambitious Holly became increasingly interested in the New York music/recording/publishing scene, while his band mates wanted to go back home to Lubbock. As a result, the group split up in late 1958. The Hollys settled in Apartment 4H of the Brevoort Apartments located at 11 Fifth Avenue in Greenwich Village. Here he recorded the series of acoustic songs, including "Crying, Waiting, Hoping" and "What to Do," known as the "Apartment Tapes," which were released after his death.

The Hollys frequented many of New York's music venues, including The Village Gate, Blue Note, Village Vanguard, and Johnny Johnson's. Maria Elena reported Buddy was keen to learn finger-style flamenco guitar, and would often visit her aunt's home to play the piano there. He wanted to develop collaborations between soul singers and rock 'n' roll, hoping to make an album with Ray Charles and gospel legend Mahalia Jackson. He also had ambitions to work in film, like Elvis Presley and Eddie Cochran, and registered for acting classes with Lee Strasburg's Actors Studio, where the likes of Marlon Brando and James Dean had trained.

According to Billy Altman's liner notes to the Geffen/Universal compilation, Buddy Holly: The Definitive Collection, in addition to "True Love Ways", during the October 1958 sessions at Decca's Pythian Temple, Holly also recorded two other songs, "It Doesn't Matter Anymore" and "Raining In My Heart." The songs were firsts for Holly, not only in the use of orchestral backing players, but also the tracks were his first stereo recordings. They were also to be his last formal recording studio sessions.

Although Holly had already begun to become disillusioned with Norman Petty before meeting Maria Elena, it was through her and her aunt Provi, the head of Latin American music at Peer-Southern, that he began to fully realize what was going on with his manager, who was paying the band's royalties into his own company's account. Holly was having trouble getting his royalties from Petty, so he hired the noted lawyer Harold Orenstein at the recommendation of his friends the Everly Brothers, who had engaged Orenstein following disputes with their own manager, Wesley Rose. Yet, with the money still being withheld by Petty and with rent due, Buddy was forced to go back on the road.

Holly was offered a spot in the Winter Dance Party, a three-week tour across the Midwest opening on January 23, 1959, by the GAC agency, with other notable performers such as Dion and the Belmonts, Ritchie Valens, and J. P. "The Big Bopper" Richardson. He assembled a backing band consisting of Tommy Allsup (guitar), Waylon Jennings (bass) and Carl Bunch (drums), and billed them as The Crickets.

Following a performance at the Surf Ballroom in Clear Lake, Iowa, on February 2, 1959, Holly chartered a small airplane to take him to the next stop on the tour. Holly, Valens, Richardson and the pilot Roger Peterson were killed en route to Moorhead, Minnesota, when their plane crashed soon after taking off from nearby Mason City in the early morning hours of February 3. There was a snowstorm, and the pilot was not qualified to fly by instruments only. Bandmate Waylon Jennings had given up his seat on the plane, causing Holly to jokingly tell Jennings, "I hope your ol' bus freezes up!" Jennings shot back facetiously, "Well, I hope your ol' plane crashes!" It was a statement that would haunt Jennings for decades. "Although the plane came down only five miles northwest of the airport, no one saw or heard the crash", wrote rock performer, archivist and music historian, Harry Hepcat, in his article about Buddy Holly. "The bodies lay in the blowing snow through the night...... February indeed made us shiver, but it was more than the cold of February that third day of the month in 1959. It was the shiver of a greater, sometimes senseless, reality invading our sheltered, partying, teenaged life of the 50's."

Holly's funeral was held on February 7, 1959, at the Tabernacle Baptist Church in Lubbock. The service was officiated by Ben D. Johnson, who had presided at the Hollys' wedding just months earlier. The pallbearers were Jerry Allison, Joe B. Mauldin, Niki Sullivan, Bob Montgomery, Sonny Curtis and Phil Everly. Waylon Jennings was unable to attend due to his commitment to the still-touring Winter Dance Party. Holly's body was interred in the City of Lubbock Cemetery in the eastern part of the city. His headstone carries the correct spelling of his surname (Holley) and a carving of his Fender Stratocaster guitar.

Holly's wife, María Elena Holly, was pregnant at the time of the crash. She miscarried the day after learning of his death, reportedly due to “psychological trauma”. Because of this incident, authorities found it necessary, in the months following, to implement a policy against announcing victims’ names until after families had first been informed. María Elena Holly did not attend the funeral, and has never visited the gravesite. She later told the Avalanche-Journal:

The first song to commemorate the musicians was “Three Stars” by Eddie Cochran. This song was recorded just one day after the disaster occurred. Twelve years later, in 1971, Don McLean released his single, "American Pie”, to commemorate Buddy Holly’s death and further accentuate the loss of the United States’ innocence. Don McLean’s song began the reference to the tragedy as "The Day the Music Died".

Holly set the template for the standard rock and roll band: two guitars, bass, and drums. He was one of the first in the genre to write, produce, and perform his own songs.

Holly managed to bridge the racial divide that marked music in America. Along with Elvis and others, Holly made rock and roll, with its roots in rockabilly country music and blues-inspired rhythm and blues music, more popular among a broad white audience. From listening to their recordings, one had difficulty determining if the Crickets, the name of Buddy's band, were white or black singers. Holly indeed sometimes played with black musicians Little Richard and Chuck Berry, and incorporated the Bo Diddley beat in several songs. The Crickets were only the second white rock group to tour Great Britain. Holly's essential eyeglasses encouraged other musicians, such as John Lennon, also to wear their glasses during performances.

In his biography of rock legend Elton John, Philip Norman recounted that by his early teens, John (then known as Reg Dwight) was wearing glasses "not because he needed them, but in homage to Buddy Holly." After wearing glasses for a while, his eyes became adjusted to the lenses, and at that point he became nearsighted and really did need glasses, which would years later establish John as one of the most famous "four-eyes" in rock and roll, though Holly is widely considered to be the first.

Contrary to popular belief, teenagers John Lennon and Paul McCartney did not attend a Holly concert, although they watched his television appearance on Sunday Night at the London Palladium; Tony Bramwell, a school friend of McCartney and George Harrison, did. Bramwell met Holly, and freely shared his records with all three. Ian Whitcomb said "Buddy Holly and the Crickets had the most influence on the Beatles." Lennon and McCartney later cited Holly as a primary influence. (Their bug-themed band's name, The Beatles, was chosen partly in homage to Holly's Crickets.) The Beatles did a cover version of "Words of Love" that was a close reproduction of Holly's version, released on late 1964's Beatles for Sale (in the U.S., in June 1965 on Beatles VI). During the January 1969 sessions for the Let It Be album, the Beatles played a slow impromptu version of "Mailman, Bring Me No More Blues" — although not written by Holly, it was popularized by him — with Lennon mimicking Holly's vocal style; the recording was eventually released in the mid-1990s on Anthology 3. Also, Holly's "That'll Be the Day", which had been covered by The Quarrymen was released on Anthology 1. In addition, John Lennon recorded a cover version of "Peggy Sue" on his 1975 album Rock 'n' Roll. McCartney owns the publishing rights to Holly's song catalogue.

A 17-year-old Bob Dylan attended the January 31, 1959 show, two nights before Holly's death. Dylan referred to this in his 1998 Grammy acceptance speech for his Time Out of Mind being named Album of the Year:

Keith Richards attended one of Holly's performances, where he heard "Not Fade Away" for the first time. The Rolling Stones had an early hit covering the song.

The launch of Bobby Vee's successful musical career resulted from Holly's death, when he was selected to replace Holly on the tour that continued after the plane crash. Holly's profound influence on Vee's singing style can be heard in such songs as "Rubber Ball" and "Run to Him."

Holly influenced many other singers during and after a career that lasted barely two years. Keith Richards once said Holly had "an influence on everybody." In an August 24, 1978, Rolling Stone interview, Bruce Springsteen told Dave Marsh, "I play Buddy Holly every night before I go on; that keeps me honest."

The Grateful Dead performed "Not Fade Away" 530 times over the course of their career, making it their seventh most-performed song. The song also appears on eight of their official live recording releases.

Various rock and roll histories have asserted the singing group The Hollies were named in homage to Buddy Holly. According to the band's website, although the group admired Holly (and years later produced an album covering some of his songs), their name was inspired primarily by the sprigs of holly in evidence around Christmas of 1962.

Don McLean's popular 1971 ballad "American Pie" is inspired by Holly and the day of the plane crash. The American Pie album is dedicated to Holly.

On September 7, 1994 (Holly's 58th birthday), Weezer released their single "Buddy Holly".

Buddy Holly released three albums in his lifetime. However, he recorded so prolifically that Coral Records was able to release brand-new albums and singles for 10 years after his death, although the technical quality was mixed, some being studio quality and others home recordings.

Buddy Holly continued to be promoted and sold as an "active" artist, and his records had a loyal following, especially in Europe. The demand for unissued Holly material was so great that Norman Petty resorted to overdubbing whatever he could find: alternate takes of studio recordings, originally rejected masters, "Crying, Waiting, Hoping" and the other five 1959 tracks (adding new surf-guitar arrangements), and even Holly's amateur demos from 1954 (where the low-fidelity vocals are often muffled behind the new orchestrations). The last new Buddy Holly album was Giant (featuring the single "Love Is Strange"), issued in 1969. Between the 1959–60 Jack Hansen overdubs, the 1960s Norman Petty overdubs, various alternate takes, and Holly's undubbed originals, collectors can often choose from multiple versions of the same song. There are also many different versions of Holly's "Greatest Hits" as well as covers/compilation albums of Buddy's songs performed by various artists.

Holly's life story inspired a Hollywood biographical film, The Buddy Holly Story (1978). Star Gary Busey received a nomination for the Academy Award for Best Actor for his portrayal of Holly. The movie was widely criticized by the rock community and Holly's friends and family for its inaccuracies. This led Paul McCartney to produce and host his own documentary about Holly in 1985, titled The Real Buddy Holly Story. This video includes interviews with Keith Richards, Phil and Don Everly, Sonny Curtis, Jerry Allison, Holly's family, and McCartney himself, among others.

In 1987, Marshall Crenshaw portrayed Buddy Holly in the movie La Bamba. He is featured performing at the Surf Ballroom and boarding the doomed airplane with Ritchie Valens and The Big Bopper. Crenshaw's version of "Crying, Waiting, Hoping" is featured on the La Bamba original motion picture soundtrack.

Buddy – The Buddy Holly Story, the Jukebox Musical depicting his life, is credited as being the first of its kind, spawning a breed of jukebox shows, including the likes of Mamma Mia! and We Will Rock You. Buddy – as it is abbreviated on occasion – is still running in the UK after 22 years, with a UK tour that went out in February 2011.

Holly was depicted in the Quantum Leap episode entitled "How the Tess Was Won" although his identity isn't revealed until the very end of the episode. According to this episode, Dr. Sam Beckett (Scott Bakula) influences Buddy Holly to change the lyrics from "piggy, suey" to "Peggy Sue", thus setting up Holly's future hit song.

There are also a number of acts both in the US (Johnny Rogers, John Mueller) and UK (Marc Robinson, Spencer J etc.) who specialize in performing Holly's songs.

In 2010, Guy Kent portrayed a modern-day interpretation of Holly in the independent film The Day the Music Died. The film has yet to be theatrically released.

Holly was based in Lubbock as his career took off between 1956 and 1958. In 1980, Grant Speed sculpted a statue of Holly playing his Fender guitar. This statue is the centerpiece of Lubbock's Walk of Fame, which honors notable people who contributed to Lubbock's musical history. Other memorials to Buddy Holly include a street named in his honor and The Buddy Holly Center, which contains a museum of Holly memorabilia as well as a Fine Arts Gallery. The Center is located on Crickets Ave, one street over from Buddy Holly Ave, in what used to be the Fort Worth and Denver South Plains Railway Depot.

In 2010, Grant Speed's statue was taken down for refurbishment, and construction began on a new Walk of Fame. On May 9, 2011, the City of Lubbock held a ribbon-cutting ceremony for The Buddy and Maria Elena Holly Plaza, the new home of the statue and the Walk of Fame. The plaza is across the street from the museum.

On September 7, 2011 (what would have been Holly's 75th birthday), he received his star on the Hollywood Walk of Fame posthumously. His widow, Maria Elena Santiago, attended, as did Phil Everly, Peter Asher, Priscilla Presley and actor Gary Busey, who played Holly in The Buddy Holly Story.