We conducted a statewide survey of freshwater mussels (family Unionidae) in wadeable streams in South Dakota in 2014 and 2015. We conducted timed searches (2 person-hours/site) at 202 sites distributed among all 14 of the state's major river drainages. We collected a total of 605 live mussels and 543 recently dead shells, representing 13 unionid species. We found mussels in each of the 14 river drainages and at 91 of the 202 sites (45%), and we collected live mussels at 22% of the sites. Species richness varied among drainages from one to 10. Mussel species richness and abundance were higher in drainages east of the Missouri River (mean richness/site = 1.2 6 0.1, mean abundance/site = 5.5 6 1.5/h) compared with western drainages (mean richness/site = 0.2 6 0.1, mean abundance/site = 0.4 6 0.2/h). The Giant Floater was the most widespread and abundant species, occurring in all 14 river drainages and representing 62.1% of all live mussels. Overall, host generalists with an opportunistic life-history strategy dominated mussel assemblages in South Dakota, which may indicate stressful conditions, particularly in western drainages. A compilation of previous records from South Dakota revealed the former presence of 32 species in the state. However, because of differences in sample effort among studies, comparison of our estimates of species richness with estimates from previous surveys at specific sites and in six eastern drainages did not reveal consistent patterns of species loss. Our use of standardized timed-search methods provides a baseline that can be used to better assess future changes in species richness and distribution and mussel abundance.