Born in Valdosta, Georgia, Bill was the son of Jim and Mary (Reese) Hicks, and had two elder siblings, Steve and Lynn. The family lived in Florida, Alabama and New Jersey, before settling in Houston, Texas, when Bill was seven. Hicks has two school-age stories on the Flying Saucer Tour Vol. 1 album. He was raised in the Southern Baptist faith, where he actually first began performing as a comedian to other children sent to Sunday School.

One pupil told Hicks' mother that "he was the funniest thing he had ever seen," which prompted Hicks' mother to question the reverend about what Bill had been saying. The reverend replied. "He's very funny but you should look at how you raise him."

Hicks never subscribed to the "valuable morals" that were preached to him. The Sunday school education he received gave him an unwavering distrust of religion which led to him adapting his own philosophy, much of which focused on ridiculing the contradictions of the brand of morality preached by institutionalised religion.

In 1990, Hicks released his first album, Dangerous, performed on the HBO special One Night Stand, and performed at Montreal's Just for Laughs festival. He was also part of a group of American stand-up comedians performing in London's West End in November. Hicks was a huge hit in the UK and Ireland and continued touring there throughout 1991. That year, he returned to the Just for Laughs festival and recorded his second album, Relentless.

Hicks made a brief detour into musical recording with the Marblehead Johnson album in 1992, the same year he met Colleen McGarr, who was to become his girlfriend and later fiancée. In November, he toured the UK, where he recorded the Revelations video for Channel 4.

The show was in contrast with the harsh and brutally frank style he had developed in reaction to the many unwelcoming and often hostile audiences of America, and shows Hicks in a playful mood and at ease with his audience. He closed the show with "It's Just a Ride", one of his most famous and life-affirming philosophies.

Later that year he recorded a stand-up performance that would become Live at Oxford Playhouse and Salvation. Hicks was voted "Hot Standup Comic" by Rolling Stone Magazine, and moved to Los Angeles in early 1993.

The progressive rock band Tool invited Hicks to open a number of concerts for them on their 1993 Lollapalooza appearances, where Hicks once famously asked the audience to look for a contact lens he'd lost. Thousands of people complied. Tool singer Maynard James Keenan so enjoyed this joke that he repeated it on a number of occasions.

In 1996, Tool released their album Ænima which contains mentions of Hicks in the liner notes and on record. The track "Ænema" references Hicks's Arizona Bay philosophy and the closing track "Third Eye" contains samples from Hicks's Dangerous and Relentless albums. Experimental rock outfit Faith No More also quoted Bill Hicks in "Ricochet" from their King for a Day... Fool for a Lifetime album, singing "It's always funny until someone gets hurt and then it's just hilarious".

In April 1993, while touring in Australia, he started complaining of pains in his side, and on June 16 of that year, he was diagnosed with liver cancer that had spread from the pancreas. He started receiving weekly chemotherapy, while still touring and also recording his album, Arizona Bay, with Kevin Booth.

He was also working with comedian Fallon Woodland on a pilot episode of a new talk show, titled Counts of the Netherworld for Channel 4 at the time of his death. The budget and concept had been approved, and a pilot was filmed. The Counts of the Netherworld pilot was shown at the various Tenth Anniversary Tribute Night events around the world on February 26, 2004.

On October 9, 1993, Hicks was scheduled to appear on the Late Show with David Letterman for the twelfth time, but his entire performance was removed from the broadcast -- the only occasion, up to that point, on which a comedian's entire routine had been cut after taping.

Both the show's producers and CBS denied responsibility. Hicks expressed his feelings of betrayal in a hand-written, 39-page letter to John Lahr of The New Yorker. Although Letterman later expressed regret at the way Hicks had been handled, he never appeared on the show again. The full account of this incident was featured in a New Yorker profile by Lahr. This profile was later published as a chapter in John Lahr's book, Light Fantastic.

Hicks played the final show of his career at Caroline's in New York on January 6, 1994. He moved back to his parents' house in Little Rock, Arkansas shortly thereafter. He called his friends to say goodbye before he stopped speaking on February 14, and died of cancer in the presence of his parents at 11:20 p.m. on February 26, 1994. Hicks was buried on the family plot in Leakesville, Mississippi.