Authorities confirmed that the two deaths occurred in the Amtrak train, not the freight train run by the CSX.
A spokesman for the South Carolina Emergency Management Division said that injuries ranged from minor cuts to broken bones, Xinhua news agency reported.
"The lead engine derailed, as well as some passenger cars," the statement said, adding: "There were eight crew members and approximately 139 passengers, with injuries reported."
The CSX confirmed the collision in the statement. No immediate information is available about the CSX train.
The Lexington County Sheriff's Department tweeted that the collision and derailment occurred near Charleston Highway and Pine Ridge Road.
The injured were in hospitals as emergency responders and police were working on the scene.
The National Transportation Safety Board said it has launched an investigation into the collision.