Given the importance of crayfish in stream ecosystems, gaining insight into the role of stream permanence in maintaining predator–prey interactions is critical. Our objectives were to determine the influence of stream permanence and season on crayfish predation and assess the role of stream permanence and crayfish density on the presence of predators, while accounting for imperfect detection. We conducted surveys of crayfish density, mammalian scat, and environmental variables within 10 intermittent and 10 permanent streams in the Ozark Highlands. We used occupancy modeling to assess the relationship between predator presence, crayfish density, and environmental variables. Stream permanence did not play a role in determining relative frequency of occurrence or percent volume of crayfish prey in mammalian diets. However, percent volume and relative frequency of crayfish prey found in scats differed by season, with both highest in spring and summer. The relative frequency and percent volume of fish prey showed a significant interaction of season by stream permanence, which may be the first instance of this observation. Procyon lotor (Raccoon) had the highest detection probability (p = 0.39), whereas Neovison vison (American Mink; p = 0.15) and Lontra canadensis (River Otter; p = 0.03) had low detection probabilities. Further study into predator–prey interactions in the context of hydrology, particularly when related to imperiled groups like freshwater crayfishes, is needed since climate change is expected to alter hydrologic patterns.