The two dead were in the same car in an eastbound lane of Interstate 10, which the Texas Department of Safety said was closed in both directions for several hours after the chain-reaction pile-up, which began about 8:30 a.m. Thursday.
Hundreds of vehicles were stuck in traffic at the scene and police were urging drivers to find alternate routes to their destinations.
The injured were taken to Christus Hospital St. Elizabeth and Baptist Hospital in Beaumont, the Medical Center of Southeast Texas, Christus Hospital St. Mary in Port Arthur, and a hospital in Baytown, Acadian Ambulance spokeswoman Denise Parker said.
She said eight people were admitted in critical condition.
The crashes -- which involved an undetermined number of 18-wheelers and at least one tanker -- occurred in the vicinity of Mile Marker 835 on the east-west highway, KBMT-TV, Beaumont, reported.
Westbound lanes of I-10 were opened at 12:38 p.m., but police said eastbound lanes would remain closed for at least 8 to 10 hours, the Beaumont Enterprise reported.