Multiple physical and biological factors contribute to the structure of freshwater mussel communities in large rivers. Mussel distributions are frequently described as clumped or patchy. However, few surveys of mussel populations have been designed to quantify these spatial patterns. We used indicators of spatial autocorrelation to quantify spatial patterns of adult and juvenile (≤ 5 years of age) freshwater mussels at local scales (i.e., < 300 m), within 14 sites along ~700 km of the Upper Mississippi River, USA. Juveniles were patchily distributed in 43% of the sites, and adults were patchily distributed in 50%. Within sites, juveniles and adults displayed the same spatial pattern in 64% of the sites. At half of the sites, hotspots of adults and juveniles overlapped suggesting spatial and temporal persistence of habitat. Mussels have an important ecological role in rivers, and information on their spatial patterns aid our understanding of the spatial structure and function of riverine ecosystems, and the ecological consequences of population declines.