The cab was hit by a northbound car shortly before 2:30 a.m. on the southbound freeway, between Old Town Avenue and Washington Street, according to the California Highway Patrol.
The other car was driven by a 42-year-old woman from Phoenix, who drove off but was later arrested.
As the cab driver was standing outside of the wrecked cab, he was struck by a car, whose driver also did not stop at the crash site, CHP officials said.
His name was not released, but the CHP said he was a local resident, also 42.
A third vehicle, a Honda Accord, then plowed into the cab, NBC7 reported.
The wrong-way driver was arrested for suspicion of several felony drunken driving charges.
The driver who fatally struck the cabbie remained at large, according to the CHP.
All southbound traffic was temporarily diverted off the freeway and a SigAlert was issued, but the lanes were reopened about 7:40 a.m.
The CHP asked anyone with information on the fatal crash to call (858) 637-3800.