Born in Lawton, Oklahoma and raised in Anaheim, California, Hillenburg became fascinated with the ocean as a child and developed an interest in art. He started his professional career in 1984, instructing marine biology, at the Orange County Marine Institute, where he wrote The Intertidal Zone, an informative comic book about tide-pool animals, which he used to educate his students. In 1989, two years after leaving teaching, Hillenburg enrolled at the California Institute of the Arts to pursue a career in animation. He was later offered a job on the Nickelodeon animated television series Rocko's Modern Life (1993–1996) after his success with The Green Beret and Wormholes (both 1992), short films that he made while studying animation.
In 1994, Hillenburg began developing The Intertidal zone characters and concepts for what became SpongeBob SquarePants. The show has aired continuously since its premiere in 1999. He also directed The SpongeBob SquarePants Movie (2004), which he originally intended to be the series finale. However, Nickelodeon wanted to produce more episodes, so Hillenburg resigned as the showrunner.
Hillenburg disclosed to Variety magazine in March 2017 that he had been diagnosed with amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease that results in the death of motor neurons in the brain and spinal cord.
Hillenburg died at his home on November 26, 2018, at the age of 57.