MacNicol won the Primetime Emmy Award for Outstanding Supporting Actor in a Comedy Series in 2001 for his role as the eccentric lawyer John Cage in the FOX comedy-drama Ally McBeal (1997–2002). He is also known for his television roles as attorney Alan Birch in the medical drama Chicago Hope (1994–98), X the Eliminator on Harvey Birdman: Attorney at Law (2000–2007), physicist Dr. Larry Fleinhardt on the CBS crime drama Numbers (2005–10), Tom Lennox in the sixth season of action-thriller 24 (2007), Doctor Octopus in The Spectacular Spider-Man (2008–09), Dr. Stark on Grey's Anatomy (2010–11), Jeff Kane on the political satire series Veep (2016–19), and Nigel the Advisor on Tangled: The Series (2017–20). He also voiced the Mad Hatter in the Batman: Arkham video game series.
MacNicol was born and raised in Dallas, Texas, the youngest of five children of Barbara Jean (née Gottlich), a homemaker, and John Wilbur Johnson, a Norwegian-American corporate executive who became an Episcopal priest later in life. He is a graduate of MacArthur High School in Irving, Texas.
MacNicol performed at the Guthrie Theater in Minneapolis for two seasons from 1978 to 1979. He appeared in productions, which included Hamlet and The Pretenders. He made his New York debut in the 1980 off-Broadway play, Crimes of the Heart. The production then moved to Broadway in 1981, and he won the Theatre World Award. It was during this production that a casting agent noticed him and audition him for a role in the film, Sophie's Choice. In 1981 he landed the starring role in his first film, Dragonslayer, opposite Ralph Richardson.

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