He is the younger brother of actresses Joan Cusack and Ann Cusack.
For Disney, Cusack played Harry in the 1985 Walt Disney Pictures film, The Journey of Natty Gann, Joey Coyle in the 1993 Hollywood Pictures film, Money for Nothing, David Shayne in the 1994 Miramax Films film, Bullets Over Broadway, Martin Q. Blank in the 1997 Hollywood Pictures film, Grosse Pointe Blank, U.S. Marshal Vince Larkin in the 1997 Touchstone Pictures film, Con Air, and Nelson Rockefeller in the 1999 Touchstone Pictures film, Cradle Will Rock.
- He was considered for the role of Obi-Wan Kenobi in Star Wars: The Phantom Menace. However, Ewan McGregor was cast at the end.
- He was one of the several actors considered to voice Woody in Toy Story. Coincidentally, his sister, Joan ended up chosen for the role of Jessie.