The Massasauga Rattlesnake (Sistrurus catenatus) occurs from extreme southeastern Canada to northern Mexico, and most populations are highly threatened due to habitat loss and fragmentation. Although their range is reduced from historical levels, they may be locally abundant in appropriate habitat. We studied movement patterns, home range and core activity centers, habitat use, and prey abundance in a robust population of Desert Massasauga Rattlesnakes (S. c. edwardsii) in southeastern Colorado by radiotracking 36 snakes over four active seasons (May–October). In the spring, snakes made long-distance directed movements (mean = 1.89 km) from the hibernacula (shortgrass, compacted clay soils) to summer foraging areas (mixed-grass/Sand Sagebrush, sandhills). Summer activity was characterized by short distance non-directional movements, and snakes were most often observed at the base of Sand Sagebrush (Artemisia filifolia). Home ranges and core activity centers were significantly larger for males than for females, but daily movements, total distance moved, and range length did not differ significantly between sexes. Prey base surveys indicated a significantly higher abundance of both rodents and lizards in summer foraging grounds than at hibernation sites. Snakes returned to the hibernaculum area in October and appeared to hibernate individually in rodent burrows. Migration patterns exhibited by S. c. edwardsii are likely resource driven, with the migratory movements observed in the spring resulting in utilization of summer foraging habitat with more abundant prey. Conversely, hibernacula with greater thermal and structural stability in the shortgrass habitat (perhaps due to the compacted clay soils versus loose sandy soils) favor migratory return for torpor in the fall. At present, the main populations in Colorado occur far from developing regions in the state, but due to habitat loss and fragmentation resulting from projected agricultural expansion and urbanization, these populations may be threatened in the future.