- Was raised by his mother's landlady in an Upstate New York boarding house after his parents were unable to care for him, an experience he wrote about in his autobiographical one-man play Lackawanna Blues.
- Decided he wanted to be an actor after playing Huck Finn in a grade school production of Tom Sawyer.
- Made his Broadway debut as Buddy Bolden in Jelly's Last Jam.
- Made his directorial debut with a production of August Wilson's Gem of the Ocean at the McCarter Theater in Princeton.
- Is friends with Halle Berry, a producer of Lackawanna Blues and his costar in Their Eyes Were Watching God.
- Wrote the adaptation for the film version of Lackawanna Blues and appears in the film in a supporting role. His twins, Lily and Trey, also have cameos.
- Gives lectures on theater at colleges and has worked as a private acting coach.
- 2005, Emmy — Outstanding Made for Television Movie: Nominee
- 1996, Tony — Actor (Featured Role--Play): Winner
- 2006, Independent Spirit Awards — Best First Feature: Nominee
- 2017, Tony — Director (Play): Nominee
- Alean Hudson — Mother
- Ruben Santiago — Father
- Lily — Daughter
- Ruben III — Son
- Jeannie Brittan — Wife
- Broderick — Son
- Trey — Son
- State University of New York, Binghamton, New York, United States (BA in Theater, 1978); Wayne State University, Detroit, Michigan, United States (MFA in Theater, 1982)