Busey’s motion picture debut was in the 1978 film Straight Time with his father Gary and Dustin Hoffman. His two most notable appearances are as the murderous religious fanatic opposite Jodie Foster in Contact and as smart-mouthed soldier Ace Levy in Starship Troopers. He appeared in H. G. Wells’ War of the Worlds, one of three 2005 film adaptations of the novel by H. G. Wells, alongside C. Thomas Howell. Additionally, he has had major roles in Tomcats opposite Jerry O’Connell and Shannon Elizabeth, in James Mangold’s thriller Identity, with C. Thomas Howell in The Hitcher II, Michael J. Fox in Peter Jackson’s The Frighteners and Road House 2. Busey played the role of “Backfire” in Patrick Durham’s movie Cross which was released directly to DVD and download in May 2011, and stars in the independent film Don’t Pass Me By.

He also provided the voice of The Radioman in the 2012 video game Spec Ops: The Line and of the DJ of Resistance Radio in XCOM 2: War of the Chosen. Additionally, he voiced Teenage Tom during flashback scenes in the 1989 film Hider in the House which his father, Gary Busey starred in as Tom Sykes.

Busey is the son of actor Gary Busey. In 2012, he and his girlfriend April had a daughter, Autumn.

In 2016, Busey starred in the feature film Deserted opposite Mischa Barton, Trent Ford, Winter Ave Zoli, Jackson Davis, Dana Rosendorff, Lance Henriksen and Gerry Bednob. The film is a psychological thriller about a group of friends on a road trip to a music festival in “Death Valley – which results in getting them hopelessly lost in the most stunning, but unforgiving topographical terrain on the planet”. Busey played the role of Clay.

In 2018, Busey appeared in two episodes of Agents of S.H.I.E.L.D. portraying Mack’s old friend Tony Caine. Busey later joined the cast of Stranger Things in the third season portraying a journalist named Bruce.