After a brief run as a recording-only project based in Austin, founding vocalist David Yow, bassist David Wm. Sims, and guitarist Duane Denison relocated to Chicago, Illinois in 1989, where they found kindred spirits in recording engineer Steve Albini and Touch and Go Records. With the addition of drummer Mac McNeilly, they began performing live, eventually attracting an international audience. Drummer Jim Kimball replaced McNeilly late in 1996, and was himself replaced by Brendan Murphy two years later.
Despite releasing a split single with leading alt-rockers Nirvana and signing to Capitol Records, the band failed to find commercial success amid the alternative rock explosion of the 1990s and disbanded in 1999. Their reunion tour ten years later garnered positive responses from audiences and critics. After breaking up again in 2010, The Jesus Lizard announced another reunion in 2017.