Morrow’s film career began when he appeared as an extra at 18 on Saturday Night Live. He co-starred alongside Johnny Depp in Private Resort (1985). Morrow played the lead role of Joel Fleischman in the award-winning television show Northern Exposure from 1990 to 1995. He left the CBS comedy-drama several episodes before its conclusion to act in movies. He starred in the critically acclaimed film Quiz Show as Dick Goodwin, a congressional investigator intent on uncovering the corruption behind the 1950s game show scandal. Morrow played the sports agent brother of Albert Brooks’ character in Mother. At one point, he was slated to play the protagonist in the 1996 film version of The Island of Dr. Moreau, but he dropped out of the project and was replaced by David Thewlis. In 2000, he directed and starred in Maze, about an artist with Tourette syndrome.

Morrow married actress Debbon Ayer on September 21, 1998.

In 2002, he played Kevin Hunter on the Showtime television series Street Time. He also appeared in the television film Custody. In 2007, he played Jack Nicholson’s doctor, Dr. Hollins, in The Bucket List. From 2005 to 2010, he starred with David Krumholtz and Judd Hirsch, playing an F.B.I. agent in Numb3rs on CBS. On March 8, 2010, it was announced that Morrow had signed on to star in Jerry Bruckheimer’s new series, The Whole Truth, on ABC. The series aired on September 13, 2010, but was pulled from the ABC schedule in December. Morrow filmed 13 episodes. Morrow starred as Henry Rearden in Atlas Shrugged: Part III, which was released September 12, 2014. In 2017, Morrow starred in the recurring role of reporter Abe Leonard in the first season of the ABC political drama Designated Survivor. He also starred in The People v. O. J. Simpson: American Crime Story as Barry Scheck. As of November 2018, news was released that a revival of Northern Exposure is in the works at CBS and that Rob Morrow will be returning as Joel Fleischman.