In May 1991, the band embarked on the two-and-a-half-year-long Use Your Illusion Tour. The following September, Guns N' Roses released the long-awaited albums Use Your Illusion I and Use Your Illusion II, which debuted at No. 2 and No. 1, respectively, on the U.S. chart, a feat not achieved by any other group. Izzy Stradlin abruptly left the band in November; he was replaced by Gilby Clarke of Candy and Kill for Thrills. Slash played his final show with Guns N' Roses on July 17, 1993. In November of that year, the band released "The Spaghetti Incident?", a cover album of mostly punk songs, which proved less successful than its predecessors. Slash then wrote several songs for what would have become the follow-up album to the Use Your Illusion twins. Axl Rose and Duff, however, rejected the material.
In 1991, Slash played lead guitar on the single "Give In to Me" off Michael Jackson's album Dangerous, as well as for the opening skit of the video for the song "Black or White" off the same album. In 1995, he played guitar on "D.S.", a controversial song from Jackson's HIStory: Past, Present and Future, Book I album, and in 1997 appeared on the song "Morphine" off the remix album Blood on the Dance Floor: History in the Mix. In 2001, Slash played on "Privacy" off Jackson's final studio album, Invincible. Slash also joined Jackson on several occasions on stage, most notably at the 1995 MTV Video Music Awards playing with Jackson on "Black or White" (and the introduction of "Billie Jean"). He made two surprise appearances during Jackson's 1992 Dangerous World Tour in Spain and Japan and supported the 1999 charity concerts MJ & Friends in Seoul and Munich playing the same set like he did for 1995's MTV Video Music Awards. The last time Slash and Jackson shared a stage was on both 2001 Michael Jackson: 30th Anniversary Special concerts in New York City playing "Black or White" and "Beat It".
In 1991, Slash collaborated with Lenny Kravitz on "Always on the Run", the lead single from Kravitz' album Mama Said. In 1993, Slash appeared on the album Stone Free: A Tribute to Jimi Hendrix, performing "I Don't Live Today" with Paul Rodgers and Band of Gypsys. Slash also guest appeared in Carole King's 1994 live concert, which was captured on her Carole King – In Concert album. Slash and King appeared on David Letterman to promote the concert. In 1996, he collaborated with Marta Sánchez to record the flamenco-inspired song "Obsession Confession" for the Curdled soundtrack. Later that year, he played with Alice Cooper at Sammy Hagar's club Cabo Wabo in Cabo San Lucas, Mexico. The show was released the following year as A Fistful of Alice. In 1997, Slash appeared alongside rapper Ol' Dirty Bastard and rock band Fishbone on Blackstreet's rock remix of their single "Fix"; he also appeared in the accompanying music video. Also in 1997, he played on the single "But You Said I'm Useless" by Japanese musician J. That same year, he contributed music to the soundtrack of Quentin Tarantino's Jackie Brown; several compositions by Slash's Snakepit can be heard throughout the film. He also appeared on the Insane Clown Posse album The Great Milenko on the track "Halls of Illusions".