The children’s program’s television network Nickelodeon issued a statement on Mr Hillenburg, who announced last year that he had been diagnosed with motor neurone disease.
The network said: “We are sad to share the news of the passing of Stephen Hillenburg, the creator of SpongeBob SquarePants. Today, we are observing a moment of silence to honor his life and work.”
In March 2017 he told Variety he was diagnosed with Lou Gehrig’s disease, also known as ALS, a progressive disease that attacks nerve cells that control the muscles and has no known cure.
Mr Hillenburg was a former marine biology teacher who launched the series featuring an animated sponge that lives in a pineapple under the sea in 1999.
As a teacher Mr Hillenburg had used illustrations of the sea and its creatures as teaching tools, with some of the characters later becoming inhabitants of Bikini Bottom, the underwater town where the show is based.
Mr Hillenburg left his teaching career to pursue an animation degree in 1987, later garnering critical acclaim for his award-winning short film Wormholes in 1992 as he earned a masters in fine arts.
Mr Hillenburg then worked at Nickelodeon on their show Rocko’s Modern Life from 1993 to 1996.
He received two Emmy Awards and six Annie Awards, from the International Animated Film Association, for SpongeBob SquarePants.
“It’s no small feat to create something as weird but unashamedly sweet and uncynical as SpongeBob. RIP,” wrote New York Times TV critic James Poniewozik in response to the news of Mr Hillenburg’s death.