Once there, Moore was briefly in the hardcore punk band Even Worse, featuring future The Big Takeover editor (and future Springhouse drummer) Jack Rabid. After exiting the band, Moore and Lee Ranaldo learned experimental guitar techniques in Glenn Branca's "guitar orchestras." He also spent much time at the University of Massachusetts and in the Amherst/Northampton area.
He and Ranaldo make extensive use of unusual guitar tunings, often heavily modifying their instruments to provide unusual timbres and drones, They are known for bringing upwards of fifty guitars to every live gig, using some guitars for one song only. In 2004, Rolling Stone magazine ranked Moore and Ranaldo the 33rd and 34th Greatest Guitarists of All Time.
He and Gordon released a few songs as Mirror/Dash, a reference to their respective nicknames. ("Mirror" being an alliterative pun on "Moore," and "Dash" being a pun on Flash Gordon.)
Moore has collaborated with scores of musicians, including Lydia Lunch, DJ Spooky, William Hooker, Christian Marclay, Mike Watt, Loren Mazzacane Connors, Tom Surgal, William Winant, Nels Cline, Cock E.S.P., Daniel Castro, Glenn Branca, Chris Corsano and My Cat is an Alien. Most of his solo/duo collaborations have been instrumental, and are generally improvised and/or noise based.
Additionally, Moore also contributed guitar work and backing vocals on "Crush With Eyeliner," which appeared on R.E.M.'s Monster LP.
Since 2004, Moore has recorded and performed with the all-star noise collective To Live and Shave in L.A., the lineup of which also features Andrew W.K.. He recorded with the band at Sonic Youth's former studio in Manhattan, and later performed with them at the George W. Bush "anti-inaugural" Noise Against Fascism concert in Washington, D.C., named in reference to Sonic Youth's 1992 song "Youth Against Fascism." Moore curated the "Nightmare Before Christmas" weekend of the All Tomorrow's Parties music festival, in December 2006.
On June 21, 2007, Moore revealed to Spin Magazine that he would be releasing a solo album titled Trees Outside The Academy. The album was recorded at J Mascis' studio in Amherst, Massachusetts. The album is made up of mostly acoustic material and features Sonic Youth drummer Steve Shelley and violinist Samara Lubelski. The album also features collaborations between Mascis and Charalambides' Christina Carter, who performs a duet with Moore on the track, "Honest James." The album was released on September 18, 2007, on Moore's label Ecstatic Peace.
On September 24, 2008, Pitchfork Media reported that Thurston was working on a song with former Be Your Own Pet vocalist Jemina Pearl. They did a cover of the Ramones song Sheena Is a Punk Rocker. The song was recorded for the teenage drama Gossip Girl, but it is unknown if the song will appear on the show, or even commercially available.
In 1994, Moore teamed up with Greg Dulli of The Afghan Whigs, Don Fleming of Gumball, Mike Mills of R.E.M., and Dave Grohl of Nirvana/Foo Fighters, to form the Backbeat Band, which recorded the soundtrack album to the movie Backbeat.
In 1998 Moore played on the soundtrack of the film Velvet Goldmine as a member of Wylde Ratttz, along with The Stooges' Ron Asheton, his Sonic Youth bandmate Steve Shelley, Minutemen's Mike Watt, Gumball's Don Fleming, Mark Arm of Mudhoney and Jim Dunbar.
Moore also composed original music for the films:
Moore reviewed new music in Arthur Magazine. He manages the website Protest Records, named for its protest against music piracy laws. Moore was the editor/overseer of the 2005 book Mix Tape: The Art of Cassette Culture.