Born in New York City in 1956, John Reiner was raised on Long Island, graduating from Smithtown High School in 1974 (and from the State University of New York in 1978). In 1974, Reiner met Mad magazine artist Mort Drucker, who encouraged him to pursue cartooning as a career. The next year he was hired by Joe Simon to work on his humor magazines. Reiner worked for Marvel Comics and did humorous illustrations and political caricatures until Drucker and Jerry Dumas hired him in 1984 to work on the King Features comic strip 'Benchley'.
He was Bill Hoest's assistant on his features from 1986, and he also co-created 'What a Guy!' with Hoest in 1987. Following the death of Bill Hoest in 1988, Reiner continued Hoest's features in collaboration with Bunny Hoest. This includes the production of the classic comic panel 'The Lockhorns', but also 'Agatha Crumm' (until 1996), 'What a Guy!' (until 1996), 'Bumper Snickers', 'Howard Huge' and 'Laugh Parade'.