Sinise was born in
Blue Island, Illinois, son of Robert L. Sinise (born 1928), a
film editor, and his wife Mylles (Alsip) Sinise (born 1928).
 His paternal grandfather was of
Italian descent, Sinise's great-grandfather Vito Sinisi having immigrated from
 Sinise briefly attended
Glenbard West High School in
Glen Ellyn, Illinois, and later graduated from
Highland Park High School in
Highland Park, Illinois,
 followed by
Illinois State University. In 1974, Sinise and two friends,
Terry Kinney and
Jeff Perry, founded the
Steppenwolf Theatre Company.
 Since then, Steppenwolf has showcased the talents of notable actors such as
Jim True-Frost, and most recently
William Petersen. Sinise honed his acting and directing skills at Steppenwolf, and received a Joseph Jefferson Award for his direction of
Lyle Kessler's play
Orphans. That took him from
New York City, and then to
West End, where he worked on more than thirty of the company's productions.