The foundation gave no official cause of death, but it's been publicly known that Simon has suffered from colon cancer since 2013.
Simon co-created the characters that would eventually become the stars of "The Simpsons" alongside Matt Groening on "The Tracey Ullman Show" in 1987. "The Simpsons" as we know it, in its half-hour animated format, debuted in December 1989. After the show's fourth season, Simon exited the production, making a deal that allowed him to found the Sam Simon Foundation and give to causes close to his heart. He donated significant sums to PETA, and the foundation bearing his name rescued dogs and trained them to assist veterans.
The thumbprint that Simon left on "The Simpsons" remains to this day; Homer and Marge are even named after members of his own real-life family. The show is currently in its 26th season. Simon, whose split with the show was not amicable, was public about the wealth he amassed from his exit deal.
"I've given most of it away," Simon told Marc Maron in 2013 on his podcast. "I won't be rich again until we get our quarterly installment from 'The Simpsons.'"
Earlier in his career, Simon was the showrunner for "Taxi," and wrote for "Cheers" and "The Drew Carey Show." He won nine Emmys throughout his career.