A Chevrolet Trailblazer was northbound on I-95 at about 7:25 p.m. Monday when it ran off the left of the highway near mile marker 177, hit a guardrail and overturned, said Trooper T.C. Wood of the state Highway Patrol.
Two women, whose names haven't been released, were thrown from the SUV and were killed. Neither was wearing a seat belt, Wood said.
Three other passengers were taken to Pitt Memorial Hospital, in Greenville, where two were listed in critical condition and the third was listed as stable.
The driver was taken to WakeMed and was listed in critical condition.
The names of the injured weren't released.
Northbound lanes of I-95 were closed for about two hours late Monday while the wreck was investigated. Southbound lanes also were closed because authorities wanted to land a medical helicopter on the highway, but they later decided to transport one of the victims by ambulance.
The six women in the SUV were traveling home to Baltimore from South Carolina, Wood said.
The wreck remains under investigation.