It happened around 7:30 Friday morning at the Republic Bank branch on the 1800 block of Market Street.
Police say the suspect walked into the bank, brandished a knife and demanded money. After getting an undisclosed amount of cash, he fled.
No one was injured during the incident.
The suspect is described as a black male in his 50s, approximately 6 feet tall with a stocky build. He was last seen wearing a tan jacket, black knit cap, and eyeglasses.
Police consider him to be armed and dangerous.
Anyone with information is urged to call the FBI at 215-418-4000 or the Philadelphia Police Department at 215-686-TIPS (8477), text a tip to PPD TIP (773847) or through PhillyPolice.com. Tipsters can remain anonymous.
Authorities say there may be a reward for information leading to the suspect's capture.