The accident happened at 3:30 a.m. Friday at the base of the Girard Point bridge near Enterprise Avenue.
Pennsylvania State Police say the tractor trailer appeared to jackknife and overturn.
Images from Sky6 showed the big rig lying on its side and southbound traffic at a standstill.
The southbound lanes were shut down for hours as crews worked to right the truck and clear the scene. Southbound traffic was being detoured off I-95 at Broad Street.
At least one southbound lane was back open after 7:00 a.m., and the scene appeared clear by 8:00 a.m.