Known for his eclectic influences and experimental projects, Patton has earned critical praise for his diverse array of vocal techniques. He has many producer or co-producer credits with artists such as John Zorn, Sepultura, Melvins, Melt-Banana, and Kool Keith. He co-founded Ipecac Recordings with Greg Werckman in 1999, and has run the label since.

Patton was born and raised in Eureka, California, where he formed Mr. Bungle, with Trey Spruance and Trevor Dunn, in 1984. During the late '80s Mr Bungle recorded the cassette-only recordings, The Raging Wrath of the Easter Bunny, Goddammit I Love America, Bowel of Chiley and OU818, featuring tracks that would later be included on their first Warner Brothers album.

Patton joined Faith No More in January 1989 replacing Chuck Mosley, who then played with Cement.

Faith No More's The Real Thing was released later that year. The album reached the top ten on the US charts, thanks largely to MTV's heavy rotation of the "Epic" music video, (which featured Patton in a Mr. Bungle T-shirt).

In the United States, Faith No More released three more studio albums; (Angel Dust, King for a Day... Fool for a Lifetime, and Album of the Year) Faith No More officially disbanded in 1998.

When interviewed about his lyrical content with Faith No More, Patton responded, "I think that too many people think too much about my lyrics. I am more a person who works more with the sound of a word than with its meaning. Often I just choose the words because of the rhythm, not because of the meaning".

During his time in Faith No More, Patton continued to work with Mr. Bungle. His success in mainstream rock and metal ultimately helped secure Mr. Bungle a record deal with Warner Bros. The band released a self-titled album (produced by John Zorn) in 1991, and the experimental Disco Volante in 1995. Their final album, California, was released in 1999.

Patton's other projects included two solo albums on the Composer Series of John Zorn's Tzadik label, (Adult Themes for Voice in 1996 and Pranzo Oltranzista in 1997). He is a member of Hemophiliac, in which he performs vocal effects along with John Zorn on saxophone and Ikue Mori on laptop electronics. This group is billed as "improvisational music from the outer reaches of madness". He has also guested on Painkiller and Naked City recordings. He has also appeared on other Tzadik releases with Zorn and others, notably as part of the "Moonchild Trio" alongside Joey Baron and Trevor Dunn, named after Zorn's album on which the trio first appeared, Moonchild: Songs Without Words.

In 1998, Patton formed the experimental metal supergroup Fantômas with Buzz Osbourne (of The Melvins), Trevor Dunn (of Mr. Bungle), and Dave Lombardo of Slayer. They have released four studio albums.

There have been several projects over the years featuring Patton that have not been officially released, although some live bootlegs do circulate. These projects include House of Discipline (with Bob Ostertag and Otomo Yoshihide), Moonraker (with Agata Ichirou of Melt-Banana, Buckethead and DJ Eddie Def), Christian Fennesz and Mike Patton, and Patton & Rahzel. Patton contributed vocals to the Team Sleep song Kool-Aid Party, but the song did not make it onto the final album.

In 2004, Patton worked with Björk and the beat boxer Rahzel on her album, Medúlla.

In 2005, Patton signed on to compose the soundtrack for the independent movie Pinion, marking his debut scoring an American feature-length film. However, this had been held up in production and may be on the shelf permanently. His other film work includes portraying two major characters in the Steve Balderson film Firecracker. He has also expressed his desire to compose for film director David Lynch.

In February 2006, Mike Patton performed an operatic piece, composed by Eyvind Kang, at Teatro di Modena in Italy. Patton sang alongside vocalist Jessika Kinney, and was accompanied by the Modern Brass Ensemble, Bologna Chamber Choir, and Alberto Capelli and Walter Zanetti on electric and acoustic guitars. Patton remarked that it was extremely challenging to project the voice without a microphone.

Patton's Peeping Tom album was released on May 30, 2006 on his own Ipecac label. The set was pieced together by swapping song files through the mail with collaborators like Norah Jones, Kool Keith and Massive Attack, Odd Nosdam, Jel, Doseone, Bebel Gilberto, Kid Koala, and Dub Trio.

In May 2007 he performed with an orchestra a few concerts in Italy, by the name of Mondo Cane, singing Italian oldies from the 50s and the 60s.

Mike also provided the voices of the monsters in the 2007 film I Am Legend starring Will Smith.

He is regarded as very hard-working. Faith No More keyboardist Roddy Bottum remarked about Patton "caffeine is the only drug he does", in reference to the Faith No More song "Caffeine" from the album Angel Dust, which Patton wrote while in the middle of a sleep-deprivation experiment. He also worked on the Derrick Scocchera short film "A Perfect Place" for the score/soundtrack, which is longer than the film itself.

In December 2008 along with Melvins, Patton co-curated an edition of the All Tomorrow's Parties Nightmare Before Christmas festival. Patton chose half of the lineup and performed the album The Director's Cut in its entirety with Fantômas. Patton also appeared as Rikki Kixx in the Adult Swim show Metalocalypse in a special 2 part episode on August 24.

In 2009 Patton created the soundtrack to the movie Crank: High Voltage. He also performed vocals on the track "Lost Weekend" by The Qemists.

On May 4, 2010 Mondo Cane, where Patton worked live with a 30-piece orchestra, was released by Ipecac Recordings. The album was co-produced and arranged by Daniele Luppi.

"Recorded at a series of European performances including an outdoor concert in a Northern Italian piazza, the CD features traditional Italian pop songs as well as a rendition of Ennio Morricone's 'Deep Down'."

Patton is known to be an avid video game player. In 2007, he provided the voice of the eponymous force in the video game The Darkness, working alongside Kirk Acevedo, Lauren Ambrose and Dwight Schultz. Patton reprised the role in The Darkness II in 2012.

He also had a role in Valve Corporation's 2007 release Portal as the voice of the Anger Sphere in the final confrontation with the insane supercomputer, GLaDOS. He has another role in the Valve title Left 4 Dead, voicing the majority of the infected zombies. He also voiced Nathan "Rad" Spencer, the main character in Capcom's 2009 video game Bionic Commando, a sequel to their classic NES title.

In February 2009, Faith No More announced that they were reforming for a tour and possibly new material, first as a footnote on a blurb for Patton's score for Crank: High Voltage and later as an official announcement on fnm.com. Their first gig on the road again was at the Brixton O2 Academy in London, where 1990's Live at the Brixton Academy was recorded, on June 10, 2009. They have played as one of three headliners at The Download Festival 2009, in Castle Donington, which was Faith No More's first time at the festival. At the festival they played "Chinese Arithmetic" with Patton humorously singing the lyrics to "Poker Face" using a beat-box effect embellishing Gaga's vocal style. Bassist Billy Gould has also stated that an American tour is "not out of the question". In June 2009 Faith No More announced that they will be headlining the NME stage at Reading & Leeds festival. On July 4, Faith No More performed a concert together at the Open'er festival in Kosakowo Airport near Gdynia, Poland.

Faith No More also played the large Roskilde Festival near the city of Roskilde, Denmark. Faith No More also performed in Portugal in Optimus Alive'10, where Mike Patton sang one song, "Evidence", completely in Portuguese. They had already played the same song completely in Italian on June 14, 2009, at the Rock in Idro Festival in Milan. 12 August 2009 was the date for FNM's first Turkish live appreance in Istanbul. On August 14, Faith no more played at the Spirit of Burgas Festival in Burgas, Bulgaria. Faith No More headlined the Australian Soundwave Festival in 2010. On the 27th of August 2009, Faith No More played in the Olympia Theatre in Dublin, Ireland and were supported by local band Adebisi Shank.

On September 1, 2009 Faith No More played at Israel Trade Fairs & Convention Center in Tel Aviv, Israel, supported by Monotonix and Dinosaur Jr. August 2009 Faith No More headlined the Radio 1/NME Stage at both Leeds & Reading Festival where they played the theme tune to popular UK Soap Eastenders as part of their setlist. On December 5, 2010, they played alongside Primus in Santiago de Chile, which was the day after their performance at the Teleton Chile. In 2011 they also performed at the Chilean Rock Concert Maquinaria on November 12 and 13, as well as at the SWU Festival on November 15.

Faith No More were to top the bill on Sunday July 8, 2012 of the Sonisphere Festival UK festival at the iconic Knebworth House venue, but on March 29, the festival was cancelled.

Patton has garnered critical praise and has been made a heavy metal icon; however, Patton's reaction to this fame has been unconventional. He has acted irreverently towards the music industry, and expressed his distaste for the infamous lifestyles of rock stars. In a 1995 interview with the San Francisco Chronicle, he stated: "It's hard to see as much as you'd like to with our schedule on the road, but it's harder to do coke and fuck whores every night. Now that's a full time job." His attitude towards popular music is also evident in his songwriting, as Allmusic critic Cammila Albertson writes: "When Patton sings 'Roll it up and smoke it again/Bottoms up and drink it again/ Fix it up and shoot it again/ I can't believe I did it again,' (Mojo by Peeping Tom) he is keenly aware of the way it sounds for such an avant-garde composer as himself to recite perfect rock & roll cliches. His lyrics mock the self-important coolness of the music industry and self parody his own place in it." His contempt for the over-the-top antics of figures in popular music is often cited as the main reason that Patton has always been so guarded about his privacy and personal life. Mike Patton has stated that he enjoyed his time in Faith No More:

Patton married Italian artist Titi Zuccatosta in 1994. They separated in 2001. During an appearance on the radio show, Loveline (Listen), Patton said that it was a case of two people wanting different things and hinted that his excessive work habits may have been a factor. "It's very hard. It's a daily struggle", he commented in regards to the rigors of juggling a busy music career and a marriage. "It had to happen... Even though we knew each other really well when we got married, it doesn't get easier." He later added, "We're trying this. See what happens. There's still hope." Patton used to own a home in Bologna, Italy (which he sold around the time of the break-up), and speaks fluent Italian. He was interviewed by music journalist Lucas H. Gordon and the answers were given by Patton in Italian.

Patton's right hand is permanently numb from an on-stage incident during his third concert with Faith No More, where he accidentally cut himself on a broken bottle and severed the tendons and nerves in his hand. He can use his hand, but he has no feeling in it (despite his doctor telling him the opposite would happen).

Patton's vocals touch on crooning, falsetto, screaming, opera, death growls, rapping, mouth music, beatboxing, and scatting, among other techniques. Critic Greg Prato of Allmusic writes, "Patton could very well be one of the most versatile and talented singers in rock music"; colleague Blake Butler called him "a complete and utter musical visionary and a mind-blowing and standard-warping genius."