Tate Donovan first gained notice for his role in the ensemble period drama Memphis Belle. Prior to that, Donovan had appeared in Space Camp and Clean and Sober. After landing his first leading role in Love Potion No. 9, he then appeared in three independent art-house features: Inside Monkey Zetterland, Ethan Fromme and Alan Rudolph's Equinox before following up with a role in the Disney family comedy, Holy Matrimony. He returned to Disney for the animated Hercules, for which he provided the vocals for the adult version of the character and has regularly reprised the role for various animated follow-up projects.

Donovan's small screen work has included a Cable ACE-nominated turn in the HBO series Vietnam War Story, the TV-movie A Case of Deadly Force (CBS) and the miniseries Nutcracker: Money, Madness, Murder (CBS). For the 1995-96 TV season, Donovan joined the parade of film stars who turned to sitcoms, heading the cast of Partners opposite Jon Cryer. He appeared in a memorable 1997 episode of NBC's Homicide: Life on the Street and had a recurring role as a client and potential love interest for Calista Flockhart's titular lawyer on Fox's Ally McBeal. He also had a recurring role as a love interest opposite Aniston in NBC's Friends and then played the priest son of a large Irish Catholic family in the short-lived 1998 NBC drama Trinity.

Next came a leading role in Christopher Coppola's G-Men from Hell and a supporting role in Swordfish. In 2003, Donovan courted a hip, young audience hit when he took on the role of dysfunctional dad in the hit Fox TV show The O.C. The actor also directed episodes of the series. In 2005, he appeared in the Vin Diesel Disney comedy The Pacifier.