The woman was driving by herself at a high rate of speed in a 2000 Toyota SUV while headed south on 101 north of Cochrane Road at about 3:14 a.m., the CHP said.
For some reason, she then turned into the center median east of the roadway, the CHP said.
Her car left the highway, smashed through a chain link fence and plunged about 25 feet into Coyote Creek that runs beneath 101, the CHP said.
The driver's side of the SUV came to rest in the creek water, which was about two feet deep, the CHP said.
CHP officers reported at 3:35 a.m. that the woman was still in the vehicle with their head underwater and they were unable to get to her.
Emergency responders reached the scene and after she was extracted from the SUV, performed CPR on her at 3:46 a.m. but soon pronounced her dead from her injuries, the CHP said.
The woman, between 25 and 45 years old, was not identified at the scene and her name will not be released until her family members are notified, the CHP said.
Officers at the CHP's bureau in Gilroy are handling the investigation into the single-car accident.
Traffic on 101 was not affected by the accident, the CHP said.