During his youth, Tisch created a number of small films with backing by Columbia Pictures. In 1976, he left Columbia and created his first feature film, Outlaw Blues. He followed this up in 1983 with Risky Business, which gave Tom Cruise his first lead role.

In 1984, Tisch produced a made-for-TV movie entitled The Burning Bed, which caused controversy but also received eleven Emmy nominations for Farrah Fawcett's depiction of a battered wife. Tisch launched his own production company in 1986, called the Steve Tisch Company, which has since specialized in small screen films. However, he also produced several critically acclaimed films including Forrest Gump, American History X, and Snatch. Tisch received a Best Motion Picture Academy Award and a Golden Globe for Forrest Gump, which was nominated for 13 Academy Awards and won six, and remains one of the 20 highest domestic box office grossing films in history. He is also the only person ever with a Golden Globe, an Academy Award, a Primetime Emmy Award nomination, and a Super Bowl Ring.

Tisch has been married twice; his first marriage ended in divorce. In 1996, Tisch married Jamie Leigh Anne Alexander. They later divorced. They had three children, two girls and a boy.

He is currently a partner in Escape Artists, an independently financed film production company based at Sony Pictures Entertainment that is the result of a merger between his Steve Tisch Company and fellow partners Todd Black and Jason Blumenthal's production company, Black & Blu. Escape Artists released The Weather Man, starring Nicolas Cage, in the fall of 2005, and The Pursuit of Happyness, starring Will Smith, was released by Columbia Pictures on December 2006. Other projects include Seven Pounds starring Will Smith, Knowing, starring Nicolas Cage and The Taking of Pelham 123 starring Denzel Washington and John Travolta.

In 2007, Tisch received the P.T. Barnum Award from Tufts University for his exceptional work in the field of media and entertainment.

Tisch was named chairman and Executive Vice President of the New York Giants American football team in 2005. Tisch accepted the Vince Lombardi Trophy twice, when the Giants won Super Bowl XLII and again when they won Super Bowl XLVI. On April 30, 2008, Tisch along with the rest of the Giants team and administration were invited by President Bush to the White House to honor the Giants Super Bowl victory.