Episodes of middle Cenozoic near-trench volcanism in California occurred during the transition from convergent to transform plate boundaries as segments of the East Pacific Rise intersected a subduction zone along western North America. Geochemical features of volcanic rocks from the Coast Range Province and Santa Maria Province, which represent two near-trench volcanic episodes, indicate that magmas from each province were derived from depleted mantle and evolved by assimilation-fractional crystallization processes to form predominantly bimodal suites. Basalt and basaltic andesite from both provinces yielded ϵNd(t) values between +9.3 and +2.4 and 87Sr/86Sr(t) ratios of 0.702 58–0.706 72. The observed ϵNd(t) values that cluster around +9 and the 87Sr/86Sr(t) ratios <0.7029 imply a source of depleted mantle, analogous to mid-ocean-ridge basalt (MORB) sources, for these rocks. Th/Ta and Ba/Ta ratios as low as 0.49 and 35.78, respectively, for the basalt are similar to those of MORB and also suggest a magma source from depleted mantle. Acidic rocks, including rhyolite, dacite, and trachyte samples have ϵNd(t) values between +6.3 and −3.2 and 87Sr/86Sr(t) ratios of 0.703 93 to 0.711 31. The variation among the Coast Range and Santa Maria Provinces volcanic rocks in Nd-Sr isotope ratio space suggests that mixing occurred between the depleted mantle-derived basaltic end-member and an incompatible-element–enriched crustal reservoir through which these rocks erupted. The observed negative correlation of ϵNd(t) and positive correlation of 87Sr/86Sr(t) ratios with SiO2, respectively, also suggest assimilation of an isotopically distinct crustal component by depleted mantle-derived melts. The ages and paleogeographic distributions of these volcanic rocks indicate that they were erupted during episodes when segments of the East Pacific Rise intersected southern California. Depleted mantle that was emplaced beneath the continental margin during ridge subduction became a source of magma for the episodes of near-trench volcanism as a new strike-slip regime evolved along the continental margin.