Mayor Michael Nutter said the death toll could rise from the derailment on the busy northeast US rail corridor as some of the 243 people on the train had not been accounted for.
He gave the injury toll as 65 but local media said it had risen to more than 140, based on a tally of people sent to local hospitals.
Herbert Cushing, the chief medical officer at Temple University Hospital, told reporters the death toll rose to six after a patient died during the night.
Shell-shocked and bleeding travelers were seen limping from the wreckage, while rescue teams with flashlights searched the seven derailed cars of the train, one of which was completely flattened.
Wheels from the train cars lay scattered by the tracks.
The cause of the crash, which came as the train negotiated a long bend, was not immediately known, although there was been no indication that it was a terrorist attack. Nutter refused to speculate on whether it was going too fast.
"I have never seen anything like this in my life."
Max Helfman, 19, was with his mother in the last car of the train, which had no seatbelts, when they suddenly felt it shake and the car then flipped over.
"People were thrown to the ground," Helfman told the Philadelphia Inquirer.
"Chairs inside the train became unscrewed and suitcases were falling on people. My mother flew into me and I literally had to catch her. People were bleeding from their head. It was awful."
Hydraulic tools had to be used to remove passengers from some of the most badly damaged train cars, firefighters said.
Former US Congressman Patrick Murphy of Pennsylvania, who was on the train, said he was sitting in the cafe car when it began to topple.
"It went to my right, then to my left. Everyone who was on the left side of the car, where I was sitting, just got thrown completely over to the right side.
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