Dozens of people were injured in the accident, which took place in the town of Chester, Pennsylvania shortly before 8:00 am (1200 GMT).
The accident occurred after "a vehicle was struck on the tracks," said Travis Thomas, fire commissioner for Chester, Pennsylvania, at a press briefing.
"There were two deceased, but they were not passengers on the train," Thomas said.
He declined to provide additional details about the accident or the victims.
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An Amtrak spokesman, Stephen Gardner, told reporters that officials from the National Transportation Safety Board were en route to the scene of the disaster to launch an investigation.
"The NTSB will provide all additional information about the crash," said Gardner, who added that workers would try to bring rail service back on line "as soon as possible."
Train service along a 30-mile (50-kilometer) stretch from Philadelphia south to Wilmington, Delaware was suspended, said Amtrak officials who did not give any indication as to when service would resume.
"Initial reports are that some passengers are being treated for injuries," Amtrak said.
"Local emergency responders are on the scene and an investigation is ongoing," it added.
Thomas said later that 35 people received hospital treatment for "non-life-threatening" injuries.
"People are being re-routed back to Philadelphia to be reunited with their luggage," he added.