Arnold was born in Ottumwa, IA, the son of Linda Kay Graham (nee Collier) and Jack Arnold. He has six siblings, Lori, Johnny, Scott, Chris, Marla and Mark. Arnold attended Ottumwa High School and began doing stand-up comedy when he was 23. He met comedienne Roseanne Barr when she saw his act in 1983. Arnold, who had Jewish ancestors named Cohen on his maternal grandfather's side, converted to Judaism upon marrying Barr.

In August 2008, Arnold broke his scapula in a motorcycle accident on the Pacific Coast Highway.

Arnold was a stand-up comic who became a writer for the popular television sitcom Roseanne (which debuted in 1988). He married the show's star, Roseanne Barr, in 1990, after she divorced her first husband. He appeared occasionally on the show as the character "Arnie Thomas" (a spoof of his name). The couple's marriage attracted media and especially tabloid attention due to their sometimes outrageous behavior. In 1992, Arnold starred in his own sitcom, The Jackie Thomas Show. Airing after Roseanne on ABC, the show lasted 18 episodes.

In 1993, Arnold and Barr bought a house together in Arnold's hometown of Ottumwa and opened a restaurant, Roseanne and Tom's Big Food Diner, in nearby Eldon, Iowa. Both appeared in the 1993 movie The Woman Who Loved Elvis, which was filmed in Ottumwa. Arnold and Barr divorced in 1994, and their restaurant closed in 1995. In a late-1990s interview on radio's Howard Stern Show, Arnold admitted that his share of his and Barr's estate amounted to "over $20,000,000," including a percentage of the Roseanne ABC-TV series, but would not elaborate further, citing a confidentiality clause.

In 1994, Arnold appeared as the sidekick to Arnold Schwarzenegger's character in the James Cameron feature film True Lies. He later supported Schwarzenegger's bid for the California governorship. His role in True Lies was parodied in an episode of The Simpsons, where washed-up actor "Troy McClure" makes a comeback in a McBain movie. The Simpsons has also shown Tom Arnold among the people sent to the Sun in a rocket, in their 10th Halloween episode.

Arnold was a host of Fox Sports Net's talk show Best Damn Sports Show Period. He has also provided the voice for the Arby's "Oven Mitt" character in television commercials for the fast-food chain.

Arnold had his first romantic leading man part in the 2005 movie Happy Endings. That same year, Arnold starred in The Kid and I, which paired him with Eric Gores, the son of billionaire Alec Gores.

Tom Arnold also hosted an episode of CMT's "The Biggest Redneck Wedding Ever." In this episode, he served as the wedding planner, and created a wedding that exceeded the dreams of a couple who wanted to be married in a mud bog.

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