Amino acids were isolated from the muscle tissue of Potamocorbula amurensis, an invasive clam species, collected from two locations in the northern portion of the San Francisco Bay. Clam specimens were collected biannually in 1997, 2002, and from 2009-2017 at both locations. The carbon and nitrogen isotope values of individual amino acids were measured. Clam specimens were collected at USGS Sites 4.1 (Suisun Bay) and 8.1 (Carquinez Strait) in the San Francisco Bay and processed as described in Stewart et al. (2013; doi:10.3354/meps10503). Amino acids were hydrolyzed from P. amurensis, derivatized, and isolated following Vokhshoori et al. (2013; doi:10.3354/meps10746). Carbon and nitrogen isotope values of individual amino acids were measured following Vokhshoori et al., 2013 and Vokhshoori and McCarthy, 2013 (doi:10.1371/journal.pone.0098087), respectively. The purpose of this study was to assess long-term changes in the biogeochemistry of the San Francisco Bay estuary following the arrival of invasive P. amurensis. Sites were selected both due to species occurrence as well as significantly different salinity ranges. This design allowed for intraspecies and site-specific variations to be explored. Nitrogen isotopes of amino acids were used to isolate variations in nutrient baseline over the twenty-year period. Carbon isotopes of amino acid were utilized to understand long-term changes in dietary sources and/or changes in the baseline carbon isotope value of the estuary's food-web.