Predicting how communities respond to multiple stressors is challenging because community dynamics, stressors, and animal-stressor interactions can vary with environmental conditions, including the intensity of natural disturbance. Nevertheless, environmental laws stipulate that we predict, measure, and mitigate the ecological effects of some human-induced stressors in the environment, including chemical contaminants in aquatic ecosystems. We conducted an experiment in Antarctica to test how a marine soft-sediment benthic community responded to multiple chemical contaminants and biotic disturbance by manipulating organic carbon enrichment, copper metal contamination, access by large epibenthic animals, and their interaction. Biotic disturbance caused mainly by large echinoderms was manipulated with exclusion cages and cage-control treatments. Colonization patterns in sediment trays revealed that total infaunal abundance and arthropods decreased with toxic Cu (0, 100, and 500 ppm) and total organic carbon (TOC; 0%, 1%, and 2% by wt), as enrichment produced increasing levels of sediment hypoxia/anoxia. Annelids and echinoderms decreased with Cu but increased with TOC because many colonizing polychaete worms, seastars, and epifaunal sea urchins were deposit feeders. Bioturbation by echinoderms disturbed sediments, leading to a substantial decline in total infaunal abundance in uncontaminated sediments, but also an increase in the relative abundance in contaminated sediments, as bioturbation mitigated the effect of both chemical stressors. Biotic disturbance also caused substantial shifts in the species composition of the invertebrate assemblages and an overall increase in species diversity. Prior predictions about the response of benthic marine phyla to the separate and combined effects of Cu and carbon enrichment appear robust to variation in natural biotic disturbance.