The fluffy white bear, known for a repetitive swimming pattern that prompted zoo officials to enrich his exhibit and give him more to do, was under anesthesia for a medical procedure after showing a low appetite and trouble chewing when veterinarians found a tumor in his thyroid.
The tumor was large and inoperable, the zoo says, and Gus was euthanized. A necropsy will be conducted to learn more about his condition.
Gus was born at the Toledo Zoo and has spent the last 25 years in Central Park. He has been seen by more than 20 million visitors in that time.
He lived about seven years longer than the average polar bear, officials said.
"Gus was an icon at the Central Park Zoo and a great source of joy for our visitors and staff," said Jim Breheny, WCS executive vice president of zoos and aquarium. "He was an important ambassador for his species bringing attention to the problems these bears face in the wild due to a changing environment."