Historical hydrographic data (1984–2012) from the California Cooperative Oceanic Fisheries Investigations (CalCOFI) program and global reanalysis products were used to quantify recent water mass variability off the coast of southern California. Dissolved oxygen concentrations continued to decline within the lower pycnocline, concurrent with strong increases in nitrate and phosphate that have spatial patterns matching those of dissolved oxygen. Silicic acid also shows an increasing trend in the offshore portion of the region, but has strong and opposing trends in the upper (increasing) and lower-pycnocline (decreasing) within the Southern California Bight. The varying rates of change in the inorganic nutrients yield a more complex pattern of variability in the nutrient ratios, resulting in large decreases in the N:P and Si:N ratios within the Southern California Bight at depths that provide source waters for upwelling. Basin-scale reanalysis products are consistent with low-frequency water mass changes observed off southern California and suggest that advection of modified source waters is the cause of the variability. The biogeochemical changes described here may have important impacts on the regional ecosystem, including a reduction of viable pelagic habitat and community reorganization.