After growing up in Bon Air, Virginia, and graduating from Midlothian High School in Richmond, Mann dropped out from Berklee College of Music in Boston to join the punk band The Young Snakes. They released the EP Bark Along with The Young Snakes in 1982. The following year, she co-founded the new wave band ‘Til Tuesday with Berklee classmate and boyfriend Michael Hausman (who went on to manage her solo career).
In 1985, the band released Voices Carry, the debut album with a title track inspired by Mann’s breakup with Hausman. It won the MTV Video Music Award for Best New Artist.
In 1986 the band released Welcome Home, their sophomore album.
In 1988, the band released Everything’s Different Now, their third and final album. Shortly after its release, Mann said that she was much more pleased with it than the debut, primarily because she felt it made more of a personal statement about her life. The band broke up in 1990 when Mann left to start her solo career.
In 1993 Mann released Whatever, her debut solo album, which sold modestly but met with critical praise. In 1995 Mann released I’m with Stupid, her sophomore album, through Geffen Records which, like her debut, garnered positive reviews but modest commercial success.
In 1997 Mann married songwriter Michael Penn (brother of actors Sean Penn and Chris Penn), whom she met in the 1980s and courted while she was recording her previous album.
In 1999 Mann recorded original material for the soundtrack to the Paul Thomas Anderson film Magnolia, which earned both Academy Award and Grammy Award nominations for the song “Save Me.” She also negotiated a contract release from David Geffen and founded her own label, SuperEgo Records.
In 2000, Mann released Bachelor No. 2, released on SuperEgo, which included some songs from Magnolia and new material. Also that year, she and her husband formed a concept called Acoustic Vaudeville, a mixture of music and stand-up comedy; among the comedians joining them for shows were Janeane Garofalo, Patton Oswalt, and David Cross.
In 2002 Mann released Lost in Space, an album which featured art by Seth. The following year she released Lost in Space Special Edition, which featured a second disc containing six live recordings (including a version of Coldplay’s “The Scientist”) as well as two B-sides and two previously unreleased songs.
In 2004 Mann released Live at St. Ann’s Warehouse, a live album and DVD recorded at a series of shows in Brooklyn.
In 2005 Mann released The Forgotten Arm, a concept album set in the 1970s about two lovers who meet at the Virginia State Fair and go on the run. The Joe Henry-produced album, which was recorded mostly live with few overdubs, contained illustrations which reflected Mann’s interest in boxing. She trained with the boxing trainer Freddie Roach; the album’s title is derived from a boxing move in which one arm is used to hit the opponent, causing him to “forget” about the other, which is then used to deliver a harsher blow. The following year Mann received a Grammy for “Best Recording Package” for the album’s artwork (shared with Gail Marowitz).
In 2006 Mann released One More Drifter in the Snow, a Christmas album featuring both covers and new songs. The album’s iTunes version replaced “Christmastime” (a duet with husband Michael Penn) with a cover of Joni Mitchell’s “River” and “Clean Up for Christmas” from The Forgotten Arm; an updated version of the CD was released two years later with the Joni Mitchell cover.
In 2008 Mann released @#%&*! Smilers, which featured Grammy-nominated artwork by Gary Taxali. The album debuted on the Billboard 200 at #32 and on the Top Independent Albums chart at #2. @#%&*! Smilers was met with mostly praise, with Billboard stating that it “pops with color, something that gives it an immediacy that’s rare for an artist known for songs that subtly worm their way into the subconscious … Smilers grabs a listener, never making him or her work at learning the record, as there are both big pop hooks and a rich sonic sheen.” The music video for the song “31 Today,” directed by Bobcat Goldthwait, featured comedienne Morgan Murphy.
In 2009 Mann announced that she was working on a musical based on her album The Forgotten Arm but later stated that it was put on hold owing to similarities to The Fighter.
In 2011 Mann joined the 9th annual Independent Music Awards judging panel to promote independent musicians. She was also an inaugural member of the panel in 2002.
In 2012 Mann released Charmer, an album which featured a duet with James Mercer of The Shins.