Amtrak train 91 -- traveling between New York and Miami -- derailed in Cayce, outside the state capital Columbia, when it collided with the CSX freight train at around 2:30 AM (1300 IST).
It was the third deadly incident involving an Amtrak train since December, raising questions about the safety of the national railway service.
Amtrak said in a statement that the lead engine derailed along with some passenger cars. Eight crew members and 139 passengers were on board.
He identified the dead as Amtrak personnel and said the freight train, which was stationary, appeared to be empty.
"It appears the Amtrak train was on the wrong track," the governor said.
"We need a conversation around the country" about rail safety, he added, after visiting passengers at a shelter set up by the local Red Cross in a school.
"As you and your loved ones gather at church and other houses of worship today, we ask that you pray for those affected and the families of those who have passed away," he said on Twitter.
"Our thoughts and prayers are with everyone that has been affected by this incident," deputy press secretary Lindsay Walters said.
The National Transportation Safety Board (NTSB) said it was investigating the incident. CSX said its personnel were on site to assist law enforcement.
The Lexington County Sheriff's Department confirmed all passengers had been evacuated.
Officials added that although 5,000 gallons of fuel spilled following the crash, the leak was contained and there was no danger to the public.
Passenger Derek Pettaway told CNN he was traveling south from Philadelphia to Orlando in a sleeper cabin when he was awoken by the impact of the crash.
"Nobody was panicking," he said. "I'm pretty sure everybody was asleep and I think people were in shock."
Pettaway added Amtrak staff had evacuated passengers in a "really calm fashion."
The Lexington County Sheriff later said four buses had been made available to take Amtrak passengers to their final destinations.
Congressman Joe Wilson called the incident "heartbreaking."
It comes just days after an Amtrak train carrying several dozen Republican lawmakers including House Speaker Paul Ryan hit a garbage truck in Virginia, killing one person and causing six others, including a congressman, to need hospital treatment.
In December, three people were killed when an Amtrak passenger train derailed in Washington state near the city of Tacoma, sending cars flying off a bridge and onto a busy interstate highway.
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