Restored grasslands are increasingly implemented to mitigate habitat loss and support biodiversity in the southeastern US, yet relatively little is known about how mammalian predators and their prey use these habitats in these areas. We evaluated patterns of site use, co-occurrence, and temporal activity of 2 mesopredators, Canis latrans (Coyote) and Lynx rufus (Bobcat), and their prey, Sylvilagus floridanus (Eastern Cottontail) and Odocoileus virginianus (White-tailed Deer), across restored grasslands in Tennessee. Using camera traps deployed across multiple sites, we quantified how predator and prey site use, co-occurrence, and temporal overlap are related to habitat features. Bobcat site use increased with greater grassland proportion in the surrounding landscape, while Eastern Cottontail site use and Bobcat–Eastern Cottontail co-occurrence were best supported by edge-related metrics, particularly forest edge density. Support for landscape effects on Coyote and White-talied Deer site use and co-occurrence was weaker. Patterns of co-occurrence suggest that predators and prey use the same grasslands sites, with some evidence of partial temporal separation between species, although limited detections of predators preclude strong inference about avoidance. Our findings highlight how structural and compositional features of restored southeastern grasslands, including edge density and proportion of grassland, may influence species’ use within broader landscapes. We acknowledge several limitations, including the small size of restored sites relative to predator home ranges, staggered camera deployments, and potential repeated detection of the same individuals. Despite these constraints, restored grasslands appear to provide habitat for both predators and prey in the southeastern US, demonstrating their potential to support mammalian communities and informing future restoration and management strategies in human-altered landscapes.