The crash happened just before 8 p.m. on Interstate 20 just west of Midland, about two miles east of the Midland-Ector county line.
Midland city spokeswoman Persephone Dakopolos says initial reports are that a thunderstorm kicked up dust that blew across the highway. Vehicles slammed into the rear of traffic slowed within the dust cloud.
Five tractor-trailer rigs were among the 17 vehicles involved. Two of the 18-wheelers sandwiched a car, killing two people inside. Battalion Chief Vince Hancock of the Midland Fire Department says two others were taken to the hospital with serious injuries.