- Trained with the American Academy of Dramatic Arts teen program and with the Colonnades Theatre Lab.
- First job was in a Colgate commercial in 1970.
- Made his Broadway debut as a replacement in the play Fifth of July in 1980, opposite Kathy Bates.
- Played Kaffee in the national tour of A Few Good Men in 1992.
- Released his first book of poetry, Swimming From Under My Father, in 2009.
- Appeared in The Library, a play directed by Steven Soderbergh, with Chloë Grace Moretz in 2014.
- 1981, Golden Globe — New Star of the Year - Actor: Nominee
- 1980, Oscar — Best Performance by an Actor in a Supporting Role: Nominee
- 2014, Screen Actors Guild Awards — Outstanding Performance by an Ensemble in a Drama Series: Nominee
- John O'Keefe — Brother
- Stephanie O'Keefe — Mother
- William O'Keefe — Brother
- Raymond O'Keefe — Father
- James O'Keefe — Brother
- Bonnie Raitt — Ex-wife
- Ann — Sister
- Mary — Sister
- Emily Donahoe — Wife
- Kevin O'Keefe — Brother
- Attended New York University, New York, New York, United States; Bennington College, Bennington, Vermont, United States (MFA in Creative Writing)