The 60-year-old victim was trapped in his apartment with his dog, KYW-TV reported. He was pronounced dead at Jefferson University Hospital.
The fire in the Walnut Square Apartments was reported at 3:42 p.m., the Philadelphia Inquirer said. Everyone in the building was evacuated.
The fire also caused massive traffic problems in Center City.
Bobby Patel, a resident, told KYW "fake alarms" are common in the building. But he said the one Wednesday "seemed real."
"I had just woken up, I work the night shift, so I woke up to a fire alarm and came down. I heard people saw water shooting down from up above," Patel said.
The dead man's identity had not been released late Wednesday. Fire officials said he was 60 and had been affected by smoke inhalation.