Virginia State Police said they responded to an RV that collided with a tractor-trailer on Interstate 66 at about 8:26 p.m. on Thursday.
According to authorities, the RV driver, Ifreke E. Inyang, 25, of Houston, faces charges of reckless driving and driving without a license.
The crash reportedly caused the RV to slide down an embankment into several trees after running off the road and hitting a guardrail.
Inyang suffered minor injuries in the crash and was transported to the hospital. Two passengers in the RV, a 39-year-old and 24-year-old, both of Houston, died at the scene, according to police.
Four other passengers suffered minor injuries, while one woman suffered-life threatening injuries.
None of the passengers in the RV were reportedly wearing seatbelts.
The semi-truck driver was also taken to the hospital for treatment for minor injuries sustained in the crash.
There is an active investigation into the crash, police said.