Kyuss' first line-up consisted of vocalist John Garcia, guitarist Joshua Homme, bassist Nick Oliveri and drummer Brant Bjork. The band gradually built a local following in Palm Desert, California and frequently performed at parties in and around the isolated towns of Southern California's desert areas. These impromptu and predominantly outdoor shows, referred to locally as "generator parties", consisted of small crowds of people, beer drinking, and the use of gasoline-powered generators to provide electricity for the equipment. Homme commented that playing in the desert "was the shaping factor for the band" noting that "there's no clubs here, so you can only play for free. If people don't like you, they'll tell you. You can't suck."
The band then signed with independent record label Dali Records, who released their debut album, Wretch, in September 1991. Several songs on the album were re-recorded versions of those that appeared on the Sons of Kyuss EP. Under-produced and poorly financed, the album was a poor representation of the "Kyuss sound", and it ultimately depicted a young band still searching for its true musical identity. Album sales were sluggish, though the band was quickly making a name for itself as a live act. Guitarist Josh Homme soon gained a reputation for his unique downtuned, psychedelic style of guitar playing, and his convention of playing electric guitars through bass guitar amplifiers to create a bass-heavy sound.
In 1992, the band, along with new producer Chris Goss, began work on their next album, Blues for the Red Sun. Goss understood the band, and was able to accurately capture their live sound in the studio. Released in June that year, the album was critically hailed and is today widely regarded as a pioneering stoner rock record. By the end of 1993, they were invited to open nine dates for Metallica touring Australia. Comparisons to stoner rock godfathers Black Sabbath became common, though Homme claimed to have little prior knowledge of the band. Bassist Oliveri left the band following completion of the album and Scott Reeder, who had been approached about joining Kyuss five-to-six months earlier during a West Coast tour with The Obsessed, made his debut at the release party for Blues for the Red Sun.
The band then soon found themselves signed with major label Elektra Records after Dali Records hit financial problems and was bought by Elektra. In 1994, they would release their first major label album, self titled "Kyuss". Originally intended to be titled Pools Of Mercury, the album commonly came to be known among fans as Welcome to Sky Valley. Between record company shuffling and bandmember shuffling it would take a whole year for the album recorded in 1993 to be released. Once again produced by Chris Goss, it received critical acclaim and, musically, demonstrated a much more psychedelic and mature sound. However, personal problems emerged and drummer Brant Bjork left the band following completion of the recording sessions. Bjork cited his extreme distaste for touring, particularly band relationship problems that develop during long periods on the road. He was replaced by Alfredo Hernández, who had previously played with Reeder in the band Across the River during the mid-80s. In July 1995, they released their fourth and final album, ...And the Circus Leaves Town. A video was made for "One Inch Man", the album's only official single. The album was not as successful commercially as Sky Valley, receiving many lukewarm reviews. Within 3 months of the release, Kyuss decided to disband sometime in October 1995. With the sudden breakup, "...And the Circus Leaves Town" received a rejuvenation in appeal and is now considered a strong effort. A compilation EP was later released in 1997 containing singles and b-sides.
After the band's breakup in 1995, there had been frequent and persistent speculation among fans regarding the possibility of a Kyuss reunion. When asked in late 2004 about whether the band would ever re-unite, Homme replied that this was unlikely to happen in the near future. However, on December 20, 2005, Garcia made a guest appearance onstage with Queens of the Stone Age during their encore at the Wiltern LG in Los Angeles. They performed three Kyuss songs together: "Thumb", "Hurricane" and "Supa Scoopa and Mighty Scoop".