A multimetric benthic assessment method was developed for two benthic assemblages in the San Francisco Estuary (USA) using data from several monitoring programs collected over five years. Assessment indicators used were total number of taxa, total abundances, oligochaete abundances, number of molluscan taxa, number of amphipod taxa, and Capitella capitata and Streblospio benedicti abundances. Exceedances of the maximum or minimum indicator values in reference samples were used to assess test samples using a weight-of-evidence to obtain an assessment value. Only 2.5% of the samples from the deeper, offshore sites had benthic impacts, 14.3% of the samples from near wastewater discharges had impacts, and 78.3% of the samples from the estuary margins and channels were impacted. Impacted samples from both assemblages had significantly higher mean effects range-median quotient values (mERMq) than reference samples, total organic carbon (TOC) was significantly higher in the impacted samples from the mesohaline assemblage, and percent fines was significantly higher in the impacted samples from the polyhaline assemblage, reflecting the close associations of contaminants with fine sediments and organic material. In samples with mERMq below 0.050, there were no benthic impacts. The incidence of impacts remained low (9.4%) at mERMq below 0.146, but when mERMq was above 0.146, 68.2% of the samples had benthic impacts, and samples with mERMq above 0.740 were always impacted.