Wilson attended the American Academy of Dramatic Arts in New York City. In 1979, he got his first “real” stage experience as a comedian.

In 1981, Wilson moved to Los Angeles to pursue his acting career. He shared an apartment with fellow aspiring comedians Andrew Dice Clay and Yakov Smirnoff, and later joked that he “taught them both about America.”

His breakthrough role was the bully Biff Tannen in the 1985 film Back to the Future. He returned in the sequels Back to the Future Part II and Back to the Future Part III to not only reprise his role as Biff, but to also play Biff’s grandson Griff Tannen and great-grandfather Buford “Mad Dog” Tannen. In every Back to the Future film, his character ends up in a pile of manure (in reality, a heap of decayed sphagnum and other mulches) after trying to kill or hurt Michael J. Fox’s character Marty McFly. He reprised his role as Biff and voiced various Tannen relatives in the animated series. Wilson did not reprise his role as Biff in the initial versions of Telltale’s Back to the Future: The Game released in 2011, being replaced by Kid Beyond. When the game was ported to the PlayStation 4, Xbox 360 and Xbox One in 2015 in commemoration of the original film’s 30th anniversary, Wilson returned to provide Biff’s voice in these newer versions.

In 1992, he voiced gangster Tony Zucco in Batman: The Animated Series and police detective Matt Bluestone in the animated series Gargoyles. He later went to co-star with Mark Hamill in Wing Commander III: Heart of the Tiger, a video game. It was the third chapter in the Wing Commander series, but the first to feature live action and was extremely popular at the time. The character played by Wilson was Major Todd “Maniac” Marshall, a fellow starfighter pilot of Hamill’s character. Wilson also starred in the sequels Wing Commander IV: The Price of Freedom (1995) and Wing Commander: Prophecy (1997) and contributed his voice to the animated series Wing Commander Academy (1996) in the same role. He also guest starred in an episode of Lois and Clark: The New Adventures of Superman in 1997.

Wilson played McKinley High School’s Coach Ben Fredricks in the 1999–2000 NBC comedy-drama Freaks and Geeks. Coach Fredricks dated Bill Haverchuck’s mother. Wilson was briefly reunited with his Back to the Future co-star Christopher Lloyd in the 1994 film Camp Nowhere.

Wilson has done voice-over work for the Nickelodeon TV show SpongeBob SquarePants. He has voiced many villainous characters that are physically strong and menacing, such as Flats the Flounder in the third-season episode The Bully, and The Tattletale Strangler in SpongeBob Meets the Strangler, and the non-villainous character Reg the Club Bouncer in No Weenies Allowed. In 2005 he played Coach Phelps in the TV series Zoey 101.

Wilson is also a painter. Many of his paintings focus on classic children’s toys. In 2006, he was selected to join the California Featured Artist Series at Disneyland. Wilson is a devout Catholic, and released a Contemporary Christian album in 2000 called In the Name of the Father.