Gary Larson was born and raised in Tacoma, Washington. His parents were Vern, a car salesman, and Doris, a secretary. He attended Curtis High School before attending Washington State University and graduated in 1972 with a degree in communications. In 1987, Larson married Toni Carmichael, an archaeologist.

Larson credits his older brother Dan for his paranoid sense of humor. Dan would pull countless pranks on Gary, taking advantage of his phobia of monsters under the bed by, for example, waiting in the closet for the right moment to pounce out at Gary. Dan is also credited with giving Gary his love of science. They caught animals in Puget Sound and placed them in terrariums in the basement; even making a small desert ecosystem, which their parents apparently did not mind. His adept use of snakes in his cartoons stems from his long-standing interest in herpetology.
Since retiring from the Far Side, Larson has occasionally done some cartooning work, such as magazine illustrations and promotional artwork for Far Side merchandise.

In 1998, Larson published his first post-Far Side book, Theres a Hair in My Dirt!: A Worms Story, an illustrated story with the unmistakable Far Side mindset.