Moore was born July 25, 1958, at Doctors Hospital in Coral Gables, Florida, to George E. Moore and Eleanor Nann Moore, and moved with his family (including brother Frederick Eugene Moore, born 1953, and sister Susan Dorothy Moore, born 1956) in 1967 to Bethel, Connecticut. He attended St. Joseph’s School in Danbury, followed by St. Mary’s School in Bethel and attended Bethel High School from 1973–76. He enrolled at Western Connecticut State University in fall 1976, but left after one quarter and moved to East 13th Street between Aves A and B in New York City to join the burgeoning post-punk and no wave music scenes. It was there that he was able to watch shows by the likes of Patti Smith and spoken-word performances by William S. Burroughs. In 1980 he moved in with Kim Gordon to an apartment at 84 Eldridge St. below artist Dan Graham, eventually befriending him, sometimes using records from Graham’s collection for mix tapes.

Moore met Kim Gordon in 1980 at the final gig of The Coachmen, the band he was in with J.D. King, Daniel Walworth (replaced by Dave Keay), and Bob Pullin. Moore, with Gordon, Anne Demarinis and Dave Keay formed a band, appearing under names like Male Bonding, Red Milk, and the Arcadians, before settling on Moore’s choice of Sonic Youth just before June 1981. The band played Noise Fest in June 1981 at New York’s White Columns gallery, where Lee Ranaldo was playing as a member of Glenn Branca’s electric guitar ensemble as well as in duo with David Linton as Avoidance Behavior. Moore invited Ranaldo, who he had known when The Coachmen shared a CBGB stage with Ranaldo’s 1970s band The Flux, to join the band. The new trio played three songs at the festival later in the week without a drummer. Each band member took turns playing the drums, until they met drummer Richard Edson. The band signed to Neutral Records, then to Homestead Records, and then to SST Records.

On June 9, 1984, Moore married Sonic Youth bassist/vocalist Kim Gordon. They have a daughter: Coco Hayley Gordon Moore (born July 1, 1994). On October 14, 2011, the couple announced that they were separating due to an extramarital affair Moore engaged in with art book editor Eva Prinz, who was also married at the time. Moore and Gordon divorced in 2013. As of 2017, Moore was residing in Stoke Newington, London, with Prinz.

Moore and other Sonic Youth members published the irreverent music zine Sonic Death. Moore runs the record label Ecstatic Peace! Beginning in 1993, this label jointly released records with rock critic Byron Coley’s label, Father Yod, as Ecstatic Yod Records.

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. Moore composed original music for such films as Heavy (1995), Bully (2001), and Manic (2001). In 2007, Moore also appeared with noise/improv group Original Silence, featuring Norwegian drummer Paal Nilssen-Love, guitarist Terrie Ex, Jim O’Rourke, saxophonist Mats Gustafsson and bassist Massimo Pupillo. The group released the live album The First Original Silence in 2007, on Oslo (Norway) label SmallTown Superjazz, and a second album The Second Original Silence in 2008.

In the early 1990s, Moore formed the side band Dim Stars, with Richard Hell, Don Fleming, Steve Shelley with a guest appearance by Robert Quine. Moore performed solo on the side stage of the 1993 Lollapalooza tour. Additionally, Moore also contributed guitar work and backing vocals on “Crush with Eyeliner”, which appeared on R.E.M.’s Monster. He played Fred Cracklin in the Space Ghost Coast to Coast episode dedicated to Sonny Sharrock. In 2000 he contributed improvised guitar pieces for a collaborative project with conceptual artist/guitarist Marco Fusinato. Since 2004, he has recorded and performed with the 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., which Moore curated, 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.

Moore 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 gig, using some guitars for one song only. In 2004, Rolling Stone ranked Moore and Ranaldo the 33rd and 34th Greatest Guitarists of All Time.

On September 18, 2007, Moore’s label Ecstatic Peace released a solo album titled Trees Outside The Academy. The album was recorded at J Mascis’ studio in Amherst, Massachusetts. The album 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.”

On September 24, 2008, Moore was working on a song with former Be Your Own Pet vocalist Jemina Pearl, a cover of the Ramones song “Sheena Is a Punk Rocker”. The song was recorded for the teenage drama Gossip Girl and was featured in the episode “There Might Be Blood”.

Since 2008, Moore has provided narration for a variety of documentaries on the National Geographic Channel. His work includes Inside: Straight Edge and the Hard Time series about life in prison.

Moore is a key figure in the popularization and resurrection of the Fender Jazzmaster. In 2009, Fender introduced a Lee Ranaldo signature edition of a Sapphire Blue Transparent version featuring two Fender Wide Range humbucking pickups and a Forest Green transparent finish for Moore, equipped with a pair of Seymour Duncan Antiquity II Jazzmaster single-coil pickups.

Ecstatic Peace Library is the book publishing company founded by Thurston Moore and visual book editor Eva Prinz in 2010. The company publishes mainly poetry, but also a collection of books about the early Norwegian black metal scene, experimental jazz from the 70s and other niche subjects.

In 2011, Moore and his wife, Sonic Youth bassist Kim Gordon, separated; shortly afterward, Sonic Youth went on indefinite hiatus. Though his marriage was ending Moore never claimed that Sonic Youth was finished.

On September 25, 2012, Moore and Kim Gordon released a collaborative album with Yoko Ono titled Yokokimthurston.

In 2012 Moore started a new band called Chelsea Light Moving. Their first track, “Burroughs”, was released as a free download. Their eponymous debut album was released on March 5, 2013. The release coincided with the 2013 SXSW Festival where they made numerous appearances including a free show at Mellow Johnny’s bike shop.

In July 2012 Moore had joined the black metal super group Twilight.

On November 24, 2013, he played guitar on “This Town Ain’t Big Enough for Both of Us” alongside Ron and Russell Mael in a Sparks concert at the Union Chapel, Islington, London.

In September 2014, Moore released The Best Day, a solo album featuring Steve Shelley and My Bloody Valentine’s Debbie Googe as rhythm section, and James Sedwards on guitar.

In 2015 Moore was appointed honorary professor at the Rhythmic Music Conservatory (RMC) in Copenhagen, Denmark, where he periodically conducts workshops and master classes.

In 2016 Yuri Landman made a special 10-string drone guitar for Moore at the request of Premier Guitar.

In April 2018, Moore presented at London’s Barbican Centre his work ‘Galaxies’, an experimental 12-string guitar ensemble. Among the twelve person orchestra were Deb Googe, Jonah Falco, Rachel Aggs, Joseph Coward and others.

In November 2019, along with other public figures, Moore signed a letter supporting Labour Party leader Jeremy Corbyn describing him as “a beacon of hope in the struggle against emergent far-right nationalism, xenophobia and racism in much of the democratic world” and endorsed him in the 2019 UK general election.