At leats 50 people are reported to be injured after the collision at roughly 2.30am, with pictures showing emergency services on the scene between Charleston Highway and Pine Ridge Road.
Before the deaths were confirmed, Amtrak has said in a statement: “Amtrak Train 91, operating between New York and Miami, came in contact with a CSX freight train at around 2.35am in Caye, South Carolina.
“The lead engine derailed, as well as some passenger cars.
“There were 8 crew members and approximately 139 passengers, with injuries reported.
“Local authorities are on the scene responding.
“More information will be provided as available”.
Early reports suggests many people are wounded.
A spokesman for Lexington sheriff confirmed in a tweet: “Train collision and derailment near Charleston Highway and Pine Ridge Road. More details to come.”
According to local media reports it is an area where they unload cars in trucks which have been transported by trains.
There is also a dog food plant not far from the site of the crash that has rail service.
The crash comes only days after another Amtrak train carrying dozens of Republican members of Congress slammed into a garbage truck in rural Virginia.
A passenger on the garbage truck, 28-year-old Christopher Foley, was killed and two others on the truck were injured, according to police.
A spokeswoman for Lexington Medical Centre said they have recieved 25 patients with minor injuries and others have been taken to level one trauma centre Polmetto Health.
No politicians were seriously injured but a Minnesota representative, Jason Lewis, was taken to a hospital as a precaution and released.
The chartered train was travelling at 61 miles per hour when the drive braked before smashing into a truck on the tracks.
The National Transportation Safety Board said in a briefing that the maximum speed limit at the grade crossing was 60 miles per hour and that the engineer in Wednesday’s crash applied the brakes 20 seconds before the train came to rest, according to preliminary information downloaded from one of the train’s event data recorders.
The NTSB is still investigating whether the train braked prior to impact.