The crash happened around 11:30 p.m. Tuesday near the intersection of Conejo and Highland.
Authorities say the driver of a black Ford Explorer was going northbound on Highland, when he swerved onto the southbound lane, crashing into a silver Toyota Corolla.
The driver of the Explorer was arrested on suspicion of DUI.
Two women were in the Corolla. They were both taken to Community Regional Medical Center with serious injuries.
Highland was closed for about an hour while the scene was cleared. The road has since been reopened.