The 25-year-old polar bear had suffered from increasing joint pain, lethargy and decreased mobility in recent months, a zoo statement said.
"Despite our best efforts to help her, Soosha's quality of life declined severely over the last few months. As hard as it is, this was the right thing to do," said Dr. Scott Larsen, the zoo's vice president of veterinary medicine.
"Soosha was adored by zoo staff and our community," said zoo spokeswoman Tiffany Barnhart. "She was the last of the iconic Denver Zoo polar bears that came to Northern Shores in 1987," a reference to a 3 1/2-acre site in the zoo that includes wildflowers, a playground and the polar bear exhibit.
Soosha arrived in Denver from a Charleston, S.C., zoo a 1-year-old, Denver's KDVR-TV reported Wednesday.
Polar bears generally live 20-25 years, the TV station noted.