Gibbons founded the Texas psychedelic group the Moving Sidewalks, which recorded several singles and one full-length album, "Flash". The Moving Sidewalks were most prominent for opening for The Jimi Hendrix Experience during the Texas leg of Hendrix's first American tour. Also notable was the Gibbons-penned song "99th Floor," its title a nod to the influence on Gibbons of fellow Texans and pioneering psychedelic band The 13th Floor Elevators. Before that, he was in a band called The Saints with fellow guitarists David Crosswell and Philip Taft.

He formed ZZ Top in late 1969 with bassist/vocalist Dusty Hill and drummer Frank Beard (both alumni of the bands American Blues, the Warlocks, and the Cellar Dwellers). After honing their trademark Texas Boogie-Blues-Rock style, they released the aptly titled "ZZ Top's First Album" on London Records in 1971.

The band rolled on, intensively touring and recording/releasing albums until 1977, when they took an extended hiatus. Their long-time manager/producer/image maker Bill Ham used this time to negotiate a deal that allowed the band to keep control of their previous recordings, to be distributed by their new label, Warner Bros. Records. They reunited two and a half years later in order to start recording under a new Warner Bros. Records contract. Unbeknownst to the other, both Dusty Hill and Billy Gibbons had grown the chest-length beards that quickly became a part of their "wildman" image. Drummer Frank Beard does not have a beard.

The band hit international prominence and their commercial peak with the release of 1983's multi-platinum-selling disc "Eliminator". Named after Gibbon's customized 1933 Ford Coupe (which, along with leggy party girls was featured in several music videos), "Eliminator" featured the hits "Legs", "Gimme All Your Lovin'", "Sharp Dressed Man" and "TV Dinners".

In 1994, the band signed a five-disc deal with RCA Records.

In 2003, a comprehensive collection of recordings from the London and Warner Bros. years entitled "Chrome, Smoke & BBQ" was released. In 2004, ZZ Top was inducted into the Rock and Roll Hall of Fame. They have the distinction of being among a very small group of bands with a 30 year plus history that still has all of its original members.

An excellent source of anecdotes, history and photos of Gibbons and his extensive car and guitar collections is the autobiographical coffee-table tome "Billy F. Gibbons-Rock + Roll Gearhead".

As of 2006, it is reported that ZZ Top is recording their 15th studio album. He also made an unforeseen appearance on the 2006 Revolting Cocks album "Cocked and Loaded."

Gibbons' most recent television performance was with The Raconteurs at the 2006 MTV Video Music Awards. Gibbons' was part of ensemble chosen to play with the band, which included Lou Reed and Jim Jarmusch. During the performance, in a sign of approval, Gibbons respectfully pointed at Jack White, a fellow blues-influenced guitarist. The performance was heavily edited and cut short by MTV for broadcast, however the full unedited performance is available on MTV's Website for the VMAs. Although not a full length performance, Gibbons can also be heard playing a few bars of the ZZ Top classic "La Grange" in the Season 2 finale of the television series Bones in which he plays, as himself, the father of series regular Angela Montenegro.