California Highway Patrol officers responded just before 1:30 a.m. Sunday to Highway 41 near Mountain View Avenue, just south of Fresno.
When officers arrived, they found two cars had crashed on southbound 41.
One driver, a woman in her 20's, suffered major injuries in the collision and was taken to Community Regional Medical Center.
The driver of the other car did not suffer any injuries.
At this time, it is unknown what caused the two cars to crash or if alcohol or drugs were factors in the crash.