Taking their name from a guitar distortion pedal, Screaming Trees recorded their first demo tape in 1985, just a few months after their formation. Their producer, Steve Fisk, was able to convince the head of Velvetone Studios to release an album by the band, The result, Clairvoyance, appeared on Velvetone Records in 1986. With Clairvoyance in hand, Fisk was able to secure Screaming Trees a contract with Greg Ginn's SST Records, who had already been releasing albums by Fisk. The band's first SST album, Even If and Especially When, was released in 1987 and the Trees began working the dying American indie circuit, playing shows across the country. The following year, SST reissued the band's demo tape under the title Other Worlds as well as their third album, Invisible Lantern.

Following the release of Buzz Factory in 1989, the group's contract with SST expired and they made the Change Has Come EP for Sub Pop early the following year. By that time, tensions in the band had grown somewhat, and the group spent most of 1990 working on side projects. Mark Lanegan recorded a solo album, The Winding Sheet, which featured support from Nirvana's Kurt Cobain and Krist Novoselic; the album appeared on Sub Pop. Both of the Conners formed new bands and released albums on the SST subsidiary New Alliance. Van's band was called Solomon Grundy; Lee's was Purple Outside. By the end of 1990, the band had signed a major-label contract with Epic Records.

Screaming Trees reconvened to record their Epic debut, Uncle Anesthesia, with Chris Cornell of Soundgarden and Terry Date as producers. Uncle Anesthesia appeared in early 1991 and, although it sold better than their previous efforts, the band remained a cult act. For much of the year, in fact, Van Conner was on hiatus from the band, choosing to tour as bassist with Dinosaur Jr. instead. Late in 1991, Nirvana's Nevermind became an unexpected commercial success, opening the gates for the rest of the Seattle scene. Where many of their peers were able to capitalize on that success, Screaming Trees suffered more setbacks than the rest. Before they began work on their follow-up to Uncle Anesthesia, Pickerel left the group and was replaced by Barrett Martin.

Once Martin joined, the band finished "Nearly Lost You," their contribution to the Singles soundtrack, and their 1992 album Sweet Oblivion. "Nearly Lost You" became a MTV and alternative radio hit in the fall of 1992, thanks to the momentum of the Singles soundtrack. The single carried Sweet Oblivion -- which had received more press attention than any previous Screaming Trees album -- to the group's strongest sales, peaking at over 300,000 copies. The band supported Sweet Oblivion with a year-long tour, during which they fought frequently. After the tour was finished, the group decided to take an extended hiatus. During that time, Lanegan recorded his second solo album, Whiskey for the Holy Ghost, which was released in 1994. That same year, Martin drummed in the Layne Staley (Alice in Chains) and Mike McCready (Pearl Jam) side project Mad Season, which released its only album in the spring of 1995.

In early 1995, Screaming Trees regrouped to begin work on their follow-up to Sweet Oblivion. Following one still-born attempt at the album, the band hired George Drakoulias, who had previously worked with the Black Crowes and the Jayhawks, as producer. The resulting album, Dust, was released in the summer of 1996, nearly four years after its predecessor. Dust was greeted with positive reviews, and its first single, "All I Know," became a moderate hit on modern rock radio. Still, the album didn't sell particularly well, even though the band supported the record by touring with 1996's Lollapalooza. Following the Dust tour, Screaming Trees took another hiatus, with Lanegan beginning work on his third solo album, Scraps at Midnight, which was released in 1998. When Lanegan completed another solo project the following year (I'll Take Care of You), it seemed to confirm that the Trees' strained relationships would make it impossible for the band to continue. Following a June 25, 2000, concert to celebrate the opening Seattle's Experience Music Project, the group unsurprisingly announced their official breakup. 2005's Ocean of Confusion: Songs of Screaming Trees 1989-1996 gathered highlights from the band's Epic years, and included two previously unreleased tracks.