Perry's musical career began in the late 1950s as a record seller for Clement Coxsone Dodd's sound system. As his sometimes turbulent relationship with Dodd developed, he found himself performing a variety of important tasks at Dodd's Studio One hit factory, going on to record nearly thirty songs for the label. Disagreements between the pair due to personality and financial conflicts, a recurring theme throughout Perry's career, led him to leave the studio and seek new musical outlets. He soon found a new home at Joe Gibbs's Amalgamated Records.

Working with Gibbs, Perry continued his recording career but, once again, financial problems caused conflict. Perry broke ranks with Gibbs and formed his own label, Upsetter, in 1968. His first major single "People Funny Boy", which was an insult directed at Gibbs, sold well with 60,000 copies sold in Jamaica alone. It is notable for its innovative use of a sample (a crying baby) as well as a fast, chugging beat that would soon become identifiable as "reggae" (the new kind of sound which was given the name "Steppers"). Similarly his acrimonious 1967 single as Lee "King" Perry Run for Cover was likewise aimed at Sir Coxsone. From 1968 until 1972 he worked with his studio band The Upsetters. During the 1970s, Perry released numerous recordings on a variety of record labels that he controlled, and many of his songs were popular in both Jamaica and the UK. He soon became known for his innovative production techniques as well as his eccentric character. In 1970 Perry produced and released The Wailers track "Mr Brown" (1970) with its unusual use of studio effects and eerie opening highlighting his unique approach to production.

In the early 1970s Lee Scratch Perry was one of the producers whose mixing board experiments resulted in the creation of dub. In 1973, Perry built a studio in his back yard, The Black Ark, to have more control over his productions and continued to produce notable musicians such as Bob Marley & the Wailers, Junior Byles, Junior Murvin, The Heptones, The Congos and Max Romeo. With his own studio at his disposal, Perry's productions became more lavish, as the energetic producer was able to spend as much time as he wanted on the music he produced. Virtually everything Perry recorded in The Black Ark was done using basic recording equipment; through sonic sleight-of-hand, Perry made it sound unique. Perry remained behind the mixing desk for many years, producing songs and albums that stand out as a high point in reggae history.

By 1978, stress and unwanted outside influences began to take their toll: both Perry and The Black Ark quickly fell into a state of disrepair. Eventually, the studio burned to the ground. Perry has constantly insisted that he burned the Black Ark himself in a fit of rage. After the demise of the Black Ark in the early 1980s, Perry spent time in England and the United States, performing live and making erratic records with a variety of collaborators. His career took a new path in 1985 when he met Mark Downie (Marcus Downbeat) with whom he worked on the 1986 album "Battle Of Armagideon" for Trojan. It was not until the late 1980s, when he began working with British producers Adrian Sherwood and Neil Fraser (who is better known as Mad Professor), that Perry's career began to get back on solid ground again. Perry also has attributed the recent resurgence of his creative muse to his deciding to quit drinking alcohol and smoking cannabis. Perry stated in an interview that he wanted to see if "it was the smoke making the music or Lee Perry making the music. I found out it was me and that I don't need to smoke."

In 1998 Perry reached a wider global audience as vocalist on the track "Dr. Lee, PhD" from the Beastie Boys' album Hello Nasty.

In 2003, Perry won a Grammy for Best Reggae Album with the album Jamaican E.T.. In 2004, Rolling Stone ranked Perry #100 on their list of the 100 Greatest Artists of All Time. More recently, he teamed up with a group of Swiss musicians and performed under the name Lee Perry and the White Belly Rats, and made a brief visit to the United States using the New York City-based group Dub Is A Weapon as his backing band. Currently there are two feature length movies made about his life and work: Volker Schaner's Vision Of Paradise and The Upsetter (film): The Life and Music of Lee Scratch Perry' by filmmakers Ethan Higbee and Adam Bhala Lough.

After meeting Andrew W.K. at SXSW in 2006, Perry invited him to co-produce his album, Repentance. The album, released on 19 August 2008, on Narnack Records, features several guest artists including Moby, Ari Up of The Slits, producer Don Fleming, drummer Brian Chippendale of Lightning Bolt and bassist Josh Werner of Matisyahu.

In 2008, Perry reunited with producer Adrian Sherwood on an album called The Mighty Upsetter. Unlike the dancehall/pop oriented Repentance, The Mighty Upsetter returned to the dub/reggae styles for which Perry is known.

Between 2007 and 2010, Perry recorded three albums with British producer, Steve Marshall. Steve had been Lee's friend and apprentice since 1984, and the albums featured performances by Rolling Stones guitarist Keith Richards, and the ubiquitous king of P-Funk, George Clinton. Two of these albums, End Of An American Dream (2008) and Revelation (2010), received Grammy nominations in the category Best Reggae Album.

In 2009, Perry collaborated with Vienna-based Dubblestandart on their Return from Planet Dub double album, revisiting some of his material from the 1970s and 1980s, as well as collaborating on new material with Dubblestandart, some of which also included Ari Up of The Slits. In 2008 leading up to this release, Perry's first foray into the dubstep genre was released on 12" vinyl, a collaboration with Dubblestandart and New York City's Subatomic Sound System called "Iron Devil". That record was followed by several more reggae oriented dubstep collaborations with Dubblestandart and Subatomic Sound System on digital and vinyl, first Blackboard Jungle Vols. 1 & 2 (2009), which featured dancehall vocalist Jahdan Blakkamoore and then Chrome Optimism (2010) which also featured American filmmaker David Lynch. Following that, in 2010, Scratch and Ari Up of The Slits on a limited edition Subatomic Sound System 7" called "Hello, Hell Is Very Low", a rootical dubstep tracks that would turn out to be one of Ari Up's last recordings and the final release during her lifetime.

In 2007, Perry's song "Enter the Dragon" was sampled on the track Carrots by Panda Bear of Animal Collective. As well, Perry was selected by Animal Collective in 2011 to perform at All Tomorrow's Parties, which the band curated in May 2011. That same year, he recorded Rise Again with bassist and producer Bill Laswell; the album features contributions from Tunde Adebimpe, Sly Dunbar, Bernie Worrell and more, and was released on Laswell's M.O.D. Technologies label.

In 2010 Lee Scratch Perry had his first ever solo art exhibition at DEM PASSWORDS art gallery in Los Angeles, California. The show entitled "Secret Education" featured works on canvas, paper, and a video installation.

In 2011 the critically acclaimed documentary film The Upsetter (film): The Life and Music of Lee Scratch Perry, narrated by Academy Award Winner Benicio Del Toro was released world wide in theaters after its premiere at the 2008 SXSW Film Festival. The film was directed and produced by American filmmakers Ethan Higbee and Adam Bhala Lough opened in Los Angeles in March 2011 and continued to screen world wide into 2012, with the DVD, ITUNES and Video On Demand release soon following

In 2012, Perry teamed with electronic music group The Orb to produce a reggae-infused album entitled The Orbserver In The Star House, which was recorded in Berlin over a period of several months. The album has earned critical acclaim and features the single "Golden Clouds", named after the historic property located near Perry’s hometown in Jamaica. In August 2012 it was announced that Perry would received Jamaica's sixth highest honour, the Order of Distinction, Commander class.

In 2013, Perry performed at the first Dub Champions Festival in Vienna, a sold out performance, backed by Dubblestandart with Adrian Sherwood handling the dub mix. Perry also performed at the first two Dub Champions Festivals in New York City in September of 2011 and again in September of 2012 backed by Subatomic Sound System. Perry performed at the 2013 Coachella Valley Music and Arts Festival in Indio, Calif.

Perry currently resides in Switzerland with his wife Mireille and two children.

Black Ark era

Post-Black Ark