There are serious concerns for native freshwater mussel survival (Bivalvia: Unionidae) in the Laurentian Great Lakes region after populations were seemingly pushed to the brink of extirpation following the introduction of dreissenid mussels (Dreissena polymorpha and D. rostriformis bugensis) in the mid-1980s. The Detroit River was the first major river system in North America to be invaded by dreissenids, and unionids were considered extirpated from the river by 1998. Since then several unionid refuges (areas with relatively low dreissenid impact and surviving unionids) have been found in coastal areas of lakes St. Clair and Erie, but no documentation exists in the Detroit River. To assess dreissenid presence and potential unionid persistence, a mixture of stratified random, historical, and potential refuge sites were surveyed during summer 2019 in the Detroit River. Unionid and dreissenid habitat use was further investigated with analysis of variance and classification tree analyses. Of the 56 sites surveyed, only five sites had live unionids totaling 220 animals of 11 species. More than 2000 unionid shells of 31 species were collected from 39 sites, confirming the large and diverse unionid populations that existed prior to the dreissenid invasion. Ninety-eight percent of live unionids found showed evidence of past or present dreissenid attachment. Estimated dreissenid densities were highly variable with river location and ranged from 0 to 5673 live individuals per m2, with the largest densities concentrated in the upstream half of the Detroit River. Despite their previously assumed extirpation from the Detroit River, live unionids were found during this comprehensive survey. Although only 40% of the historical species within the unionid assemblage remains, our results suggest, in the right conditions, some coexistence is possible among some species of unionids and dreissenids in this large river system.