Firefighters responded to the scene near the Avenue 52 exit in the Highland Park area of Los Angeles around 1:30 a.m.
Authorities performed a physical rescue to remove the five women from the 2011 Nissan Sentra.
Anagraciela Cuadra, 22, and Blanca Belman Almanza, 23, were pronounced dead at the scene.
The driver, a 23-year-old resident of San Gabriel, was transported to Los Angeles County USC Medical Center. The two other victims were transported to Huntington Memorial Hospital in Pasadena. All three were listed in serious condition following the crash.
The northbound freeway remained shut down until shortly after 5:30 a.m.