The crash was reported at 10:27 a.m. on Foothill Expressway, just south of Page Mill Road.
Witnesses said the victims were headed south on Foothill Expressway when the woman, who was behind the wheel, allowed the car to drift left into another southbound lane, Palo Alto police Agent Kara Salazar said.
The car struck another southbound vehicle then ricocheted to the right, left the roadway and crashed head-on into a tree, Salazar said.
The two were trapped in the car, and it took firefighters about 40 minutes to extricate them, Salazar said.
They were taken to Stanford Hospital, where they were both listed in critical condition.
No one in the other car was injured.
Anyone with information about the crash is asked to call police at