Jabari, a 28-year-old male western lowland gorilla, died Friday afternoon while under anesthesia.
The zoo said Jabari had lost his appetite in recent days, and starting Thursday he showed signs of mouth or throat discomfort.
After the zoo's veterinary team anaesthetized Jabari to examine him, he stopped breathing. Attempts to resuscitate him were unsuccessful.
The zoo is conducting a necropsy to determine the cause of the gorilla's illness and death.
Jabari was born at the Brookfield Zoo in Chicago on February 5, 1985, and came to the Philadelphia Zoo from the St. Louis Zoo on July 13, 2004. The group Jabari lived with with most recently included Honi, an 18-year-old female, and Kira, a 14-year-old female.
The zoo said during his nine years in Philadelphia, Jabari was one of the its most beloved animals, and the largest animal in PECO Primate Reserve. Most recently, he garnered attention for his potential to breed with Kira, and father the first gorilla born at the Zoo in many years.
He was featured on Wednesday's edition of the Action News Outdoor Adventure at the Zoo hosted by meteorologist Cecily Tynan.
In a statement, Dr. Andy Baker, Chief Operating Officer at the Philadelphia Zoo, said, "We are shocked and deeply saddened by this tremendous loss. Jabari was an iconic favorite with our staff and visitors, and we expected him to be with us for many years."
The zoo said gorillas may live as long as 50 years in zoos, with a more typical lifespan in the mid-30's. The Philadelphia Zoo's Massa held the longevity record of 54 years at the time of his death in 1984.