In 1985, Brickell was invited to sing one night with friends from her high school in a local folk rock group, New Bohemians. She would join the band as lead singer. After the band was signed to a recording contract, the label changed the group's name to Edie Brickell & New Bohemians. Their 1988 debut album, Shooting Rubberbands at the Stars, became a critical and commercial success, including the single "What I Am." The band's follow-up album, Ghost of a Dog (1990), was a deliberate effort to highlight the band's eclectic personality and move away from the pop sensibility of their first record.
Brickell had a role as a folk singer in the 1989 film Born on the Fourth of July. Her version of Bob Dylan's "A Hard Rain's a-Gonna Fall" is featured on the film's Soundtrack. She also sang a cover version of Lou Reed's "Walk on the Wild Side" in the 1990 film Flashback.
Brickell married singer-songwriter Paul Simon on May 30, 1992. Brickell was performing on NBC's Saturday Night Live on November 5, 1988, when she noticed Simon standing in front of the cameraman. "Even though I'd performed the song hundreds of times in clubs, he made me forget how the song went when I looked at him. We can show the kids the tape and say, 'Look, that's when we first laid eyes on each other.'" Brickell and Simon have three children: Adrian, Lulu, and Gabriel.
As a solo Artist, Brickell released Picture Perfect Morning (1994) and Volcano (2003). The video for Picture Perfect Morning's "Good Times" was included as part of the multimedia samples featured on Microsoft's Windows 95 Companion CD-ROM. In 1992, she worked with Producer Bob Wiseman in New York and Toronto on a collection of songs, utilizing a wind ensemble, unusual keyboards, and Ron Sexsmith. The songs were rejected by the record company and remained unreleased. In 2006, with all of the original members of New Bohemians, she made another album titled Stranger Things.
In 2010, Brickell became a founding member of new band The Gaddabouts, consisting of Steve Gadd on drums, Edie Brickell as lead vocalist and guitar, Andy Fairweather Low on electric and acoustic guitars and background vocals, Pino Palladino on bass and guitar, and featuring Dan Block, Ronnie Cuber, Joey DeFrancesco, Gil Goldstein, and Marcus Rojas. In 2011, Brickell wrote the title track, "The Meaning of Life," for Tamar Halpern's film, Jeremy Fink and the Meaning of Life.
Starting in May 2013, she toured with Steve Martin and the Steep Canyon Rangers throughout North America.
In 2016, the musical Bright Star — to which she contributed music, lyrics, and story — opened on Broadway at the Cort Theatre.
In 2017, Brickell and Martin appeared in the award-winning documentary film The American Epic Sessions directed by Bernard MacMahon. They recorded “The Coo Coo Bird”, a traditional English folk song, live on the first electrical sound recording system from the 1920s. The track appeared on the accompanying Soundtrack, Music from The American Epic Sessions.
