The violent crash was reported at about 5:20 a.m. near Atlantic Avenue, prompting the closure of all eastbound lanes for several hours, according to the California Highway Patrol.
CHP started receiving 911 calls about a wrong-way driver speeding west in the eastbound lanes 10 minutes before the deadly crash.
Police say the wrong-way driver - a 21-year-old Palmdale woman driving a Honda sedan - crashed into a 30-year-old Hemet woman driving in the carpool lane.
Both drivers died at the scene.
The freeway was closed nearly six hours for the investigation.
All lanes were reopened shortly before 11 a.m., Caltrans said.