The woman was exiting eastbound Interstate Highway 380 at about 3:50 a.m. when her vehicle was struck by another car headed south on El Camino Real, police said.
The driver of the second vehicle, a 21-year-old man from San Bruno, fled the scene and was taken into custody at his home at about 5:30 a.m.
The crash shut down El Camino Real between Sneath Lane and San Bruno Avenue for about eight hours.
The victim's name is being withheld until her family is notified, San Mateo County Coroner Robert Foucrault said.
Investigators had not determined whether drugs or alcohol played a role in the crash.