"It is with much sadness that we must let you know that Sam Simon has passed over," the message read. "We all miss him, and in his honor, we will continue bringing his vision to light through our work at The Sam Simon Foundation. We take comfort in knowing how many greetings he is receiving across that Rainbow Bridge. We love you Sam!"
Another Facebook page for his foundation added, "He passed away peacefully in his own bed, in his own home, surrounded by people and a dog who loved him."
The creative mind behind one of the longest, most successful shows in TV history had been vocal about his battle with the disease that eventually took his life. One of his last tweets was March 1 when he shared a picture of him at the doctor's getting his lungs drained.
Simon, who was a Los Angeles native, was diagnosed in 2012 and been given just months to live. In the three years he dealt with the disease, he kept his fans updated via social media and his pictures in the hospital were always candid and showed his humor in dealing with cancer.
In an interview last year with Vanity Fair, Simon was open about giving his fortune - upwards of $100 million -- away to charities that were close to his heart, including animal rights. Simon was fiercely protective of all animals -- bears, chimps, dogs, dolphins and elephants. He also started a program called Feeding Families, which was a vegan food bank for 400 families in California.
Simon, who co-created "The Simpsons" with Matt Groening and James L. Brooks in the late 1980's, told the magazine how his obsession with helping other causes began.
"I'm an atheist, but there's a thing called tithing that a lot of religions do. Ten percent was the minimum you were supposed to give to charity every year. And I always outdid that," he said.
Carolyn Miles, president and CEO of Save the Children, said Simon supported the organization for decades.
"He gave a voice to children and endangered animals who can't speak up for themselves," Miles said. "And he gave away his fortune so that they may have a chance at a better life.
"Sam once told me: 'Giving -- I get pleasure from it. I love it. I don't feel like it's an obligation. In fact, nothing is as gratifying as knowing that my giving has changed lives, especially the lives of children,'" she said.
He was such a large donor to organizations like PETA that the organization named a headquarters after him.
After news of his death broke, PETA President Ingrid Newkirk told ABC News in a statement "I think Sam died with a smile on his face, knowing that elephants were on their way out of the circus, something that, together with the closure of SeaWorld, he dreamt of and talked about all the time. He said the last two years of his life, since his diagnosis, were his happiest, as he used them to help animals who had nothing, and it gave him great joy to see chimpanzees, elephants, and even a "gay" bull find freedom from harm because he had worked with PETA to get them all out of hideous circumstances."
It was his missions and causes that inspired Simon and kept him moving forward long past the date doctors assumed he would have passed.
"My doctors have never said they can cure me," he told Vanity Fair. "They are extending my life and doing a remarkable job of it. My scans from back when I was diagnosed, my doctor said, 'If I showed these scans to my colleagues, half of them would say you're dead, and half would say you're immobile and can't get out of bed.'"
But he never saw what he was doing to help animals and others as work or "philanthropy at all. This is part of my therapy. I'm pacing my life looking forward to these things, and I enjoy them. I enjoy bringing my friends ... I like to live my life with these goals ahead of me. But it also has to do with alleviating suffering."
Simon was married twice in his life, once to actress Jennifer Tilly from 1984 to 1991 and also to Playboy Playmate Jami Ferrell in 2000.