Police said the collision involved two cars and was reported at 7:28 a.m. at the intersection of University Avenue and Highway 84.
Officers arrived at the scene to find the driver of one of the cars suffering from major injuries and the driver of the second car with possibly life-threatening injuries, according to police.
Both women were taken to Stanford Hospital for treatment.
Police said the crash appears to have happened when one of the drivers went over the median from an eastbound lane of University Avenue into oncoming traffic on the westbound side.
Both westbound lanes of traffic on University Avenue and left-hand turn lanes from Highway 84 onto University are closed as police investigate the crash.
Motorists are advised to use alternate routes.