Invasive organisms can have significant impacts on native species, and the San Francisco Estuary (SFE), California, USA, is one of the world's most invaded estuaries. Decline of native white sturgeon Acipenser transmontanus abundance in the SFE has been acknowledged, but underlying mechanisms are poorly understood. Invasion by the overbite clam Potamocorbula amurensis has drastically altered the SFE benthic prey community, yet little is known about how this change has affected sturgeon diets. We investigated changes in the diet of white sturgeon following the overbite clam invasion and subsequent shift in the SFE benthic prey assemblage. Gut content analysis was used to compare white sturgeon prey composition and importance between the pre- and post-invasion periods. Additionally, stable isotope analysis was employed to estimate the assimilation of prey items to sturgeon biomass. Overbite clams dominated diets in the post-invasion period, accounting for 82 to 93% of total volume. Stable isotope analysis confirmed the importance of this prey item, although their assimilated contribution to sturgeon biomass was estimated to be less (70 to 83%) than gut contents indicated. The frequency of fish in white sturgeon guts increased in the post-invasion period, and isotope analysis indicated relatively large contributions of fish to sturgeon biomass (3.7 to 19%). The trophic adaptability of white sturgeon has allowed them to exploit this new prey source (overbite clam). Future conservation and restoration efforts must consider a potentially destabilized food web given the large importance of a single prey item.