Joe was awarded the Tony and Joseph Jefferson Award for his acclaimed performance as Richard Roma in David Mamet's Pulitzer Prize-winning play Glengarry Glen Ross. Some of Joe's film and television highlights are House of Games, Searching for Bobby Fisher,Godfather III, the role of Dean Martin in The Ratpack, and the voice of Fat Tony on The Simpsons. For two seasons Joe stared with Mary Steenburgen and Amber Tamblyn in the critically acclaimed CBS drama Joan of Arcadia, winner of the 2004 People Choice Award for best new drama as well as picking up three Emmy nominations. In 2008, Joe reprised his Emmy nominated role of Lou Manahan opposite Debra Messing in USA Network series The Starter Wife. In April of 2011, Joe received a star on the Hollywood Walk of Fame.

Joe has completed the feature films The Bronx Bull, Ten Cent Pistol and Compulsion. He is also co-producer of a documentary on the late science fiction icon, Ray Bradbury. Joe also stars as FBI Special Agent David Rossi in the Hit CBS Drama Criminal Minds as well as hosting and producing duties on "Gun Stories" for the Outdoor Channel.

In May of 2012, Joe was appointed the National Spokesperson for The U.S. Army Museum, to lead the fundraising campaign to build the long-planned National Museum of the United States Army.

“Abraham Lincoln once said, 'To care for him who shall have borne the battle and for his widow and his orphan.' No one does more to live by these words than the Gary Sinise Foundation. For that reason, I’m proud to be an ambassador of this exemplary organization.”

— Joe Mantegna