It happened around 8:30 p.m. Thursday at Market and Juniper streets.
Police say a 63-year-old man was driving in a white Lincoln SUV near City Hall when he lost control and jumped a curb.
A man in his 50s and another in their 30s were waiting to cross the street when they were struck, police said.
Police say the driver took off after the crash but was later arrested on the 1700 block of North Broad Street.
Chopper 6 video shows officers surrounding the vehicle that was heavily damaged after the crash.
"Officers were able to pull out of the vehicle a 63-year-old man who displayed clear signs of intoxication. He was taken into custody," said Inspector D.F. Pace.
The driver will be charged with DUI and leaving the scene of an accident.
Police say the man in his 50s lost his leg, while the victim in his 30s suffered serious injuries to his lower body.
Inspector Pace says it doesn't appear the victims knew each other.
Anyone with information on the crash is asked to call police at 215-686-TIPS.