- Enrolled in an acting class at age 10.
- At 13, made his TV debut playing Roddy Miller in the CBS series Windows on Main Street, then went on to appear in episodes of Leave It to Beaver and My Three Sons.
- Was the original voice of Johnny Quest on Hanna-Barbera's animated series The Adventures of Johnny Quest.
- In 1968, served in the United States Marine Corps Reserves.
- Joined the L.A. improv-comedy troupe the Groundlings in 1976.
- Breakout role was playing Eric "Otter" Stratton in National Lampoon's Animal House (1978).
- Made his directing debut in 1984 with an episode of NBC's St. Elsewhere.
- Was co-owner and chair of the humor magazine National Lampoon from 1989 to 1991.
- 2003, Emmy — Outstanding Guest Actor in a Drama Series: Nominee
- 2002, Emmy — Outstanding Guest Actor in a Drama Series: Nominee
- 2016, Critics' Choice Awards — Best Actor in a Movie Made for Television or Limited Series: Nominee
- Molly Lewis Matheson — Daughter
- Jennifer Leak — Ex-wife
- Megan Murphy — Ex-wife
- Clifford — Father
- Sally — Mother
- Emma Katherine Matheson — Daughter
- Sue — Sister
- Cooper Timothy Matheson — Son
- Attended California State University, Northridge, California, United States
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