The news was confirmed by Nickelodeon, which has broadcast the hugely popular cartoon series since 1999.
In a statement, the company said Hillenburg’s cause of death was motor neurone disease (also known as ALS– a condition he revealed he had been diagnosed with in March last year.
As well as creating the character, Hillenburg also directed 2004’s The SpongeBob SquarePants Movie.
“We are sad to share the news of the passing of Stephen Hillenburg, the creator of SpongeBob SquarePants,” Nickelodeon tweeted from its official account.
“Today, we are observing a moment of silence to honour his life and work.”
The company’s statement added: “Steve imbued ‘SpongeBob SquarePants’ with a unique sense of humour and innocence that has brought joy to generations of kids and families everywhere.
“His utterly original characters and the world of Bikini Bottom will long stand as a reminder of the value of optimism, friendship and the limitless power of imagination.”
Hillenburg is survived by his wife of 20 years, Karen Hillenburg, and son Clay.
The SpongeBob SquarePants series has seen more than 200 episodes broadcast and has spawned two successful animated films.