Cantrell has also collaborated and performed with Heart, Ozzy Osbourne, Metallica, Pantera, Circus of Power, Metal Church, Gov't Mule, Damageplan, Pearl Jam, the Cult, Stone Temple Pilots, Danzig, Glenn Hughes, Duff McKagan, and Deftones, among others.

[18] He also contributed to the soundtracks of The Cable Guy (1996), John Wick: Chapter 2 (2017), and Dark Nights: Metal (2018), and he has made cameos in films such as Jerry Maguire (1996), Rock Slyde (2009), and Deadwood: The Movie (2019).

[22] His father is an Army veteran, and his mother was an amateur organist and melodica player who worked as an administrative assistant for the Clover Park School District in Pierce County, Washington.

Downing, David Gilmour, Nancy Wilson,[46] and Eddie Van Halen as major influences,[47] as well as Elton John[48] and bands Fleetwood Mac,[48] Heart[46][49] and Rush as his early songwriting idols.

[52] In 1985 or 1986, Cantrell moved back to Tacoma and began a band called Diamond Lie, which included singer Scott Damon, drummer Bobby Nesbitt and bassist Matt Muasau.

[57] Three weeks after his mother's death on April 11, 1987, Cantrell went to see the band Alice N' Chains perform at the Tacoma Little Theatre, and was impressed by the voice of the lead singer, Layne Staley.

[75] Cantrell started to sing lead vocals on the 1992 acoustic EP Sap, and his role continued to grow in the following albums, making Alice in Chains a two-vocal band.

[102][38] Alice in Chains performed four shows supporting Kiss on their Alive/Worldwide Tour in 1996, including the final live appearance of Layne Staley on July 3, 1996, in Kansas City, Missouri.

The band reformed in 2005 when drummer Sean Kinney had the idea to reunite the surviving members[104] to perform a benefit concert for the victims of the tsunami disaster that struck South Asia in 2004.

[105] On February 18, 2005, Cantrell, Mike Inez and Sean Kinney reunited to perform for the first time in 10 years as Alice in Chains at the K-Rock Tsunami Continued Care Relief Concert in Seattle.

[106] The band featured Damageplan vocalist Pat Lachman, as well as other special guests including Maynard James Keenan of Tool, Wes Scantlin from Puddle of Mudd and Ann Wilson of Heart.

[109] Between 2006 and 2007, Cantrell played in a number of concerts with Alice in Chains featuring guest lead singers such as Ann Wilson,[110] Mark Lanegan,[111] James Hetfield,[112] Phil Anselmo,[112] Billy Corgan,[111] Scott Weiland[113] Sebastian Bach,[114] and William DuVall.

[118] Comes with the Fall was both the opening act on Cantrell's tour for his second solo album, Degradation Trip, and also the singer's backing band,[119] with DuVall singing Staley's parts at the concerts in 2001 and 2002.

[115][121][122] By April 2007, Alice in Chains had been writing and demoing songs for a new album with DuVall,[123] but the band did not show further signs of progress until October 2008, when they announced that they had begun recording with producer Nick Raskulinecz in the studio.

His first solo material was the song "Leave Me Alone", released exclusively on The Cable Guy soundtrack in 1996, featuring Alice in Chains drummer Sean Kinney on drums and Cantrell on lead vocals, guitar and bass.

[21][160] Finally in June 2002, Cantrell issued his second solo album, Degradation Trip, with Ozzy Osbourne's then live rhythm section, Mike Bordin (drums) and Robert Trujillo (bass).

Performing mostly cover songs from bands like Led Zeppelin, AC/DC, The Stooges, Black Sabbath, and Aerosmith, the group was rounded out by vocalist John Corabi, bassist Chris Wyse, and drummer Josh Howser.

[220] On December 9, 2011, Cantrell joined Metallica for their 30th anniversary concert at The Fillmore in San Francisco and performed the songs "For Whom the Bell Tolls", "Nothing Else Matters", "Seek and Destroy" and a cover of Lynyrd Skynyrd's "Tuesday's Gone".

[224] Cantrell alongside Pearl Jam's Mike McCready and Soundgarden's Chris Cornell, also played guitar for Heart's hit song "Barracuda" with Ann and Nancy Wilson at the ceremony.

[228] On March 13, 2017, Cantrell made a guest appearance at Steel Panther's concert at The Roxy Theatre in West Hollywood and performed "Man In The Box" with the band joined by Godsmack singer Sully Erna on lead vocals.

[231] Cantrell sang "Love Her Madly" accompanied by The Doors' original guitarist Robby Krieger, keyboardist George Laks, bassist Zander Schloss, and drummer Brian Young.

[232] On December 8, 2017, Cantrell joined The Hellcat Saints (a supergroup featuring members of The Cult, Velvet Revolver, Weezer and Apocalyptica), to open for Jane's Addiction at the third annual Rhonda's Kiss benefit concert at the Hollywood Palladium in Los Angeles.

[234] On January 16, 2019, Cantrell along with William DuVall, Pearl Jam's guitarist Stone Gossard and bassist Jeff Ament, and drummer Josh Freese performed Soundgarden's "Hunted Down" at the Chris Cornell tribute concert "I Am the Highway".

[271][272] In January 2019, Dunlop released a new version of the pedal, with a design based on Cantrell's tribal orca tattoo created by Coast Salish artist Joe Wilson, and lyrics for the Alice in Chains song "Rainier Fog" on the bottom plate.

[292] In the early 1990s, Cantrell and his Alice in Chains bandmates Layne Staley and Mike Starr were featured on the music video "Never a Know, But the No", from the Seattle thrash metal band Forced Entry.

[28] Cantrell would later pay tribute to Cornell during the Rock and Roll Hall of Fame ceremony on April 14, 2018, joining singer Ann Wilson for a rendition of Soundgarden's "Black Hole Sun".

[335][336][337] In 1996, Cantrell became involved with anti-racism organisation Artists for a Hate Free America,[338] alongside other musicians including Jeff Ament, Beck and Michael Stipe, to film public service announcements, and pose for a national ad campaign.

[338] On April 12, 2004, Cantrell and his then-band Cardboard Vampyres performed at a benefit concert for Sweet Relief, a nonprofit organization that helps needy musicians cover medical expenses.

[339] In 2007, Cantrell auctioned off some of his favorite clothes from key moments in his career to benefit MusiCares and the Layne Staley Fund,[340][341] which provides support and treatment for heroin recovery in the Seattle music community.

[349] In 2015, Alice in Chains donated two dollars from every pre-sold ticket of their summer tour to help the family of a fan named Stefan Dayne-Ankle, who died after a battle with leukemia.