Williams spent much of his early career playing drums in punk rock bands. In 1996, mounting child support payments led Williams to capitalize on his family name and sign a contract with Nashville, Tennessee music industry giant Curb Records. Three Hanks: Men With Broken Hearts was issued shortly thereafter, which spliced together recordings to make it seem that three generations of Williams men were singing alongside one another.

Williams' first solo album, Risin' Outlaw, was released in September 1999 to respectable sales and strong reviews. While his name (and his uncanny vocal and physical resemblances to his grandfather) could have guaranteed Williams a thriving country audience, he did not have patience for the often predictable Nashville sound, nor for even the minimal constraints on behavior his promoters required. His opinions on this subject are well summed up in the songs "Trashville" and "Dick in Dixie"; Lovesick, Broke and Driftin' was released in 2002.

Known for his relentless touring, Williams' live shows typically follow a "Jekyll and Hyde" format: a country set, followed by a hellbilly set, and then an Assjack set. He plays country and hellbilly with his "Damn Band" and produces a very different sound with Assjack, which is a punk rock band. The lineup for Assjack includes the addition of supplemental vocalist, Gary Lindsey, bassist JoeBuck switching from upright to electric bass, and the departure of his fiddle and slide guitar players. In the past, The Damn Band/Assjack also featured fiddle-player extraordinaire Michael "Fiddleboy" McCanless, who would play both sets, adding traditional violin for country set of the concert before plugging his instrument into an amplifier and distortion unit for later sets. Another former band member was guitarist Duane Denison, previously with The Jesus Lizard, who left The Damn Band and Assjack in January 2001 and later that year formed Tomahawk.

Williams had a great deal of trouble with Curb Records. He expressed dissatisfaction with his debut, and reportedly the label was unwilling to release his appropriately named This Ain't Country LP, nor allow him to issue it on another record label. In response, Williams began selling t-shirts stating "Fuck Curb." Also during this era, Williams played bass guitar in Superjoint Ritual, a now defunct band led by with former Panteravocalist Phil Anselmo. Joe Fazzio, former drummer for Superjoint Ritual, has toured with Hank III as well as contributing to his album Lovesick, Broke and Driftin'.

In late 2004, Thrown Out of the Bar was slated for release, but Curb opted not to issue it. Williams and label executive Mike Curb would be in and out of court for the next year before a judge ruled in favor of Williams in the spring of 2005, demanding that Curb release the album. Shortly thereafter, Williams and Curb came to terms, and Williams dropped his "Fuck Curb" campaign. Bar was reworked into Straight to Hell, released on Curb’s rock imprint, Bruc, which featured a cover of "Pills I Took," originally by Those Poor Bastards.

Battles with Wal-Mart had delayed the release of Straight to Hell, which was released on February 28, 2006 as a two-disc set in two formats: a censored version (for Wal-Mart), and an uncensored version, which was the first major-label Country album to bear a parental advisory warning.

Hank released Damn Right, Rebel Proud on Oct. 21, 2008.