For Disney, he is best known for voicing John Smith in the 1995 Disney animated feature film Pocahontas. However, his younger brother Donal took over the role in the 1998 direct-to-video sequel Pocahontas II: Journey to a New World. He also played Tom Mullen in the 1996 Touchstone Pictures film Ransom, and Rev. Gramham Hess, in the 2002 Touchstone Pictures film Signs. He also directed Apocalypto.
- Mel Gibson was originally considered for the role of Ego in Guardians of the Galaxy Vol. 2, but at the end, Kurt Russell was cast instead.
- He was considered for the role of Obi-Wan Kenobi in Star Wars: The Phantom Menace.
- He was approached for the role of Odin in Thor, but turned it down, in the end, the role went to Anthony Hopkins.
- He was considered for the role of Wolverine in X-Men (2000) along with Glenn Danzig, Russell Crowe, Dougray Scott, Keanu Reeves, Gary Sinise, Aaron Eckhart, Jean-Claude Van Damme, Viggo Mortensen, Edward Norton, and Bob Hoskins.