Named San Pablo Avenue for almost its entire length except for its northernmost 0.10 miles (0.16 km), SR 123 is a major north–south state highway along the flats of the urban East Bay.

San Pablo Avenue itself, a portion of Historic US 40, continues well past the SR 123 designation south to Downtown Oakland and north to Crockett.

The express bus line was put in place after a Metropolitan Transportation Commission study determined that it would be more cost-effective than a previous proposal to install light rail along the route[citation needed].

The Bay Area Rapid Transit system runs its Richmond leg parallel to the route up to the El Cerrito del Norte station.

It originated in the Spanish colonial era as the Camino de la Contra Costa ("road of the opposite shore", i.e. opposite from the Presidio of San Francisco and the settlement around the Mission in San Francisco) and was legally a "camino real"[4] ("royal road", i.e., property of the Spanish crown) until Mexico won its independence in 1821.

It ran from the Encinal ("Oakland") landings of the Rancho San Antonio northward (actually northwestward) along the bayshore, then eastward just inland of the Carquinez Strait.

Portions of San Pablo Avenue, particularly in Berkeley, Albany, and El Cerrito, are slowly transforming, with a mix of shops, restaurants and condominium developments.

Except where prefixed with a letter, postmiles were measured on the road as it was in 1964, based on the alignment that existed at the time, and do not necessarily reflect current mileage.