He is known for film roles such as insurance agent Ned Ryerson in Groundhog Day[1] and amnesiac Sammy Jankis in Memento, as well as such television characters as Commissioner Hugo Jarry in Deadwood, Bob Bishop in Heroes, Sandy Ryerson in Glee, Stu Beggs in Californication and White Famous, "Action" Jack Barker in Silicon Valley, Dr. Leslie Berkowitz in One Day at a Time, Principal Earl Ball in The Goldbergs, and Dr. Schulman in The Mindy Project.

[3] He grew up creating imaginative games with his brother, and his story The Dangerous Animals Club paints a picture of how unsupervised children in the 20th century could amuse themselves.

[5] He is a cousin of former Dallas attorney Ira Tobolowsky,[6] who was murdered in his home in 2016 by a disgruntled former litigant.

He has also worked in the theater, directing and acting in plays in New York City, San Francisco, and Los Angeles.

[11] Tobolowsky was nominated for a Tony Award for Best Performance by a Featured Actor in a Play for the 2002 revival of Morning's at Seven.