[1] After graduating from college, Hirsch served in the United States Army Reserve in 1958 at Fort Leonard Wood for six months as a surveyor.

[13] The Los Angeles Times noted that Hirsch is "one of the very few actors who slips effortlessly from TV series to Broadway to feature films and back again, racking up awards and favorable reviews wherever he performs.

[2] After appearing frequently on television in the 1970s, including one season (1976–1977) in the series Delvecchio,[15] Hirsch gained stardom for his lead role of Alex Rieger in the popular sitcom Taxi, which ran from 1978 to 1983.

[17] After Taxi, Hirsch played the title character on the modestly successful sitcom Dear John and in 1989 won a Golden Globe Award for Best Actor in a Television Series in a Comedy or Musical for this role.

[20] Hirsch has guest-starred on episodes of Warehouse 13, Studio 60 on the Sunset Strip, Law & Order: Special Victims Unit, God Friended Me, and The Whole Truth (he reunited with Numb3rs co-star Rob Morrow), among others and lent his voice to the animated programs Tom Goes to the Mayor and American Dad!

In 2016, Hirsch appeared on the CBS comedy series The Big Bang Theory portraying the father of Johnny Galecki's character, Leonard.

[15] In early 2020, Hirsch appeared in a scene as the historic Simon Wiesenthal, in season 1, episode 8 of the Amazon Prime Video show Hunters, which stars Al Pacino.

[23] Other noteworthy stage performances include The Hot l Baltimore, Talley's Folly, and his starring role in I'm Not Rappaport, for which Hirsch also won a Tony Award in 1986.