Generator Rex is based on the comic M. Rex, created by Aaron Sowd, Joe Kelly and Duncan Rouleau and published by Image Comics in 1999.

The series was created by Man of Action for Cartoon Network, with John Fang of Cartoon Network Studios serving as supervising producer.

The show aired 60 episodes in total, but two additional episodes were produced and never aired.

Episodes 56 through 60 were made available for purchase on iTunes before they actually aired on television.

A two-part crossover special titled Ben 10/Generator Rex: Heroes United aired on November 25, 2011, featuring Ben Tennyson and Rex teaming up against a villain created by Rex's older brother Caesar, the Alpha Nanite.

A second crossover special, Ben Gen 10, aired on April 11, 2021, presenting younger and different versions of the Generator Rex characters set within the Ben 10 universe.

Rex makes a cameo appearance in the OK K.O.! Let's Be Heroes episode 'Crossover Nexus' alongside many other Cartoon Network shows.

A video game, Generator Rex: Agent of Providence, was released in 2011 for multiple platforms with the entire TV series voice cast reprising their roles, and it was scored by the show's composer Kevin Manthei.

Mattel produced a toy line based on the series, and MEGA Bloks announced a construction set line in 2010, though some planned figure waves were never released.