Cornell was born and raised in Seattle, Washington and attended Shorewood High School. His parents are Ed Boyle (a pharmacist from an Irish Catholic background) and Karen Cornell (an accountant from a Jewish background). He has five siblings: older brothers Peter and Patrick, and younger sisters Katy, Suzy, and Maggie. Peter, Katy and Suzy all performed in the band Inflatable Soule in the 1990s. Peter is currently the frontman for the New York-based rock band Black Market Radio. Katy performs as lead vocalist for the Seattle band Happy Hour Hero.

Cornell spent a two-year period between the ages of nine and eleven solidly listening to The Beatles after finding a large collection of Beatles records abandoned in the basement of a neighbour's house. Cornell was a loner; however, he was able to deal with his anxiety around other people through rock music. Before becoming a successful musician, he worked at a seafood wholesaler and was a sous chef at a restaurant named Ray's Boathouse.

In the early 1980s, Cornell was a member of a cover band called The Shemps that performed around Seattle. The Shemps also featured bassist Hiro Yamamoto. Following Yamamoto's departure from The Shemps, the band recruited guitarist Kim Thayil as its new bassist. Cornell and Yamamoto stayed in contact, and after The Shemps broke up Cornell and Yamamoto started jamming together, eventually bringing in Thayil to join them.

Soundgarden was formed in 1984 by Cornell, Thayil and Yamamoto with Cornell originally on drums and vocals. In 1985, the band enlisted Scott Sundquist as the drummer to allow Cornell to concentrate on vocals. The band's first recordings were three songs that appeared on a compilation for C/Z Records called Deep Six. In 1986, Sundquist, who by that point had a wife and a child, decided to leave the band and spend time with his family. He was replaced by Matt Cameron, the drummer for Skin Yard, who became Soundgarden's permanent drummer.

Soundgarden signed to Sub Pop, releasing the Screaming Life EP in 1987 and the Fopp EP in 1988 (a combination of the two was issued as Screaming Life/Fopp in 1990). Though the band was being courted by major labels, in 1988 they signed to SST Records to release their debut album, Ultramega OK (1988), for which they earned a Grammy Award nomination for Best Metal Performance in 1990. The band subsequently signed with A&M Records, becoming the first grunge band to sign to a major label. In 1989, the band released their second effort, and their first for a major label, Louder Than Love. Following the release of Louder Than Love, Yamamoto left the band to finish his Master's degree in Physical Chemistry at Western Washington University. He was replaced by former Nirvana guitarist Jason Everman. Everman was fired following Soundgarden's tour supporting Louder Than Love. In 1990, the band was joined by a new bassist, Ben Shepherd.

Along with Alice in Chains, Nirvana, and Pearl Jam, Soundgarden became one of the most successful bands from Seattle's emerging grunge scene in the early 1990s. With Shepherd, the new line-up recorded Badmotorfinger in 1991. The album brought the band to a new level of commercial success, and Soundgarden found itself amidst the sudden popularity and attention given to the Seattle music scene. Badmotorfinger included the singles "Jesus Christ Pose", "Outshined", and "Rusty Cage". The three singles gained considerable airtime on alternative rock radio stations, while the videos for "Outshined" and "Rusty Cage" gained considerable airtime on MTV. The song "Jesus Christ Pose" and its music video was the subject of widespread controversy in 1991, and the video was removed from MTV's playlist. "Rusty Cage" was later covered by Johnny Cash on his 1996 album, Unchained. It also appeared on the fictional radio station Radio X on the video game Grand Theft Auto: San Andreas and in the 32-bit version of Road Rash. "Room a Thousand Years Wide" was released previously as a single in 1990, but not to promote the album. It was released (with the song "HIV Baby") as a 7" through Sub Pop's Single of the Month club a full year before the release of Badmotorfinger. The song was re-recorded for this album. Badmotorfinger was nominated for a Grammy Award for Best Metal Performance in 1992. It was also ranked number 45 in the October 2006 issue of Guitar World on the magazine's list of the 100 greatest guitar albums of all time.

Superunknown became the band's breakthrough album. Upon its release in March 1994, Superunknown debuted at number one on the Billboard 200. The album launched several successful singles, including "Spoonman" and "Black Hole Sun", and granted Soundgarden international recognition. Superunknown achieved quintuple platinum status in the United States, triple platinum status in Canada, and gold status in the United Kingdom, Sweden, and the Netherlands. Rolling Stone gave Superunknown four out of five stars. Reviewer J.D. Considine said Superunknown "demonstrates far greater range than many bands manage in an entire career." He also stated, "At its best, Superunknown offers a more harrowing depiction of alienation and despair than anything on In Utero." Considine criticized "Black Hole Sun" and "Half", stating that the former is "not a very good song" while the latter "is the virtual definition of a B-side." Jon Pareles of The New York Times said that "Superunknown actually tries to broaden its audience by breaking heavy-metal genre barriers that Soundgarden used to accept." He added that "Soundgarden...want[s] something different from standard heavy metal." David Browne of Entertainment Weekly gave the album an A. He said, "Soundgarden is pumped and primed on Superunknown, and they deliver the goods." He praised it as a "hard-rock milestone-a boiling vat of volcanic power, record-making smarts, and '90s anomie and anxiety that sets a new standard for anything called metal." The album was nominated for the Grammy Award for Best Rock Album in 1995. Two singles from Superunknown, "Black Hole Sun" and "Spoonman", won Grammy Awards, and the music video for "Black Hole Sun" won a MTV Video Music Award and a Clio Award. Superunknown was ranked number 336 on Rolling Stone magazine's list of the 500 greatest albums of all time, and "Black Hole Sun" was ranked number 25 on VH1's list of the 100 greatest songs of the '90s.

The band's final album was 1996's self-produced Down on the Upside. The album spawned several singles, including "Pretty Noose", "Burden in My Hand", and "Blow Up the Outside World". The album was notably less heavy than the group's preceding albums, and marked a further departure from the band's grunge roots. Soundgarden explained at the time that it wanted to experiment with other sounds. David Browne of Entertainment Weekly said, "Few bands since Led Zeppelin have so crisply mixed instruments both acoustic and electric." However, tensions within the group arose during the sessions, with Thayil and Cornell reportedly clashing over Cornell's desire to shift away from the heavy guitar riffing that had become the band's trademark. Despite favorable reviews, the album did not match the sales of Superunknown. In 1997, Soundgarden received another Grammy nomination, for the lead single "Pretty Noose". Due to tensions within the band, reportedly due to internal strife over its creative direction, Soundgarden announced it was disbanding on April 9, 1997. In a 1998 interview, Thayil said, "It was pretty obvious from everybody's general attitude over the course of the previous half year that there was some dissatisfaction."

In 1998, Cornell began working on material for a solo album on which he collaborated with Alain Johannes and Natasha Shneider of the band Eleven. The album, entitled Euphoria Morning, was released on September 21, 1999. The album proved commercially unsuccessful although the album's single "Can't Change Me" was nominated for Best Male Rock Vocal Performance at the 2000 Grammy Awards. Euphoria Morning includes "Wave Goodbye", Cornell's tribute to his late friend Jeff Buckley. It has been noted that Euphoria Morning is influenced by Buckley's songwriting and distinctive vocal style. He also contributed the song "Sunshower" (a bonus track on the Japanese release of Euphoria Morning) to the soundtrack of the 1998 film, Great Expectations, and a reworked version of the track "Mission", retitled "Mission 2000", was used on the soundtrack to the 2000 film, Mission: Impossible II. In 2000, Cornell embarked on a tour in support of the album.

Audioslave was formed after Zack de la Rocha left Rage Against the Machine and the remaining members were searching for another vocalist. Producer and friend Rick Rubin suggested that they contact Cornell. Rubin played the remaining Rage Against the Machine band members the Soundgarden song "Slaves & Bulldozers" to showcase his ability. Cornell was in the writing process of a second solo album, but decided to shelve that and pursue the opportunity to work with Tom Morello, Tim Commerford and Brad Wilk when they approached him. Morello described Cornell: "He stepped to the microphone and sang the song and I couldn't believe it. It didn't just sound good. It didn't sound great. It sounded transcendent. And... when there is an irreplaceable chemistry from the first moment, you can't deny it." The quartet wrote 21 songs during 19 days of rehearsal and began working in the studio in late May 2001.