We examined recent faunal changes in freshwater mussels (Unionidae) in northern Ohio. We assessed species diversity in 2 agricultural watersheds, the Vermilion and Huron Rivers, and compared these faunas among 7 neighboring rivers within the Lake Erie watershed that varied in levels of human impact, geological structure, and fish diversity. We found 19 mussel species in each of the Huron and Vermilion Rivers, and 89% of species overlapped between the 2 rivers. Museum records suggested that as many as 4 species might now be missing from each river, and across the 9 tributaries in the region, species loss has been common. The total number of species once present in each river was positively correlated with watershed area, but the size of watersheds no longer provides a significant estimate of mussel or fish diversity. Current mussel faunas also were weakly correlated with the fish species present, suggesting that mussel species ranges have not been limited by a lack of available fish hosts.