The aquarium announced the death Tuesday, the Chicago Sun-Times reported. Rio was 21.
Rio came to the aquarium as a pup from the Little Rock, Ark., zoo. She was a fixture in the At Home on the Great Lakes exhibit.
"It's been a remarkable experience watching Rio inspire our guests throughout her years at the aquarium. As she grew older, Rio became a testament to the zoological community's emerging expertise in geriatric animal care and welfare," Ken Ramirez, executive vice president of animal care and training, told the newspaper. "With her playful personality, Rio was a beloved ambassador for her species."
River otters came close to extinction in Illinois because of habitat loss, water pollution and trapping. In recent years, they have become more common.
Rio had enjoyed a much longer life than she likely would have been in the wild, where most river otters die by the age of 12. Shedd officials said she was suffering from arthritis and other problems of old age and clearly "feeling very poorly."