We describe the diet of Desert Massasauga, Sistrurus catenatus edwardsii, in Arizona, Colorado, and New Mexico using fecal remains and gut contents obtained from field encounters and museum specimens. From these, 165 prey were identified, including 97 (58.8%) lizards, 51 (30.9%) mammals, 15 (9.1%) centipedes (Scolopendra sp.), one (0.6%) anuran, and one (0.6%) snake. Analyses of geographic, sexual and ontogenetic variation within S. c. edwardsii suggest diet is homogeneous among populations and between the sexes but that juveniles consume significantly more lizards and fewer mammals than adults. We assess rangewide variation in diet of Sistrurus catenatus using our data from Arizona, Colorado, and New Mexico (S. c. edwardsii) and previously published studies of populations in Wisconsin (Sistrurus catenatus catenatus), Michigan (S. c. catenatus), Missouri (Sistrurus catenatus tergeminus) and Texas (S. c. tergeminus) as well as new data from Texas (S. c. tergeminus). Significant geographic variation in diet parallels ecological and behavioral variation across the range of S. catenatus. Sistrurus c. edwardsii are xeric grassland-adapted snakes dependent on lizard and centipede prey, whereas both eastern subspecies favor more mesic environs and prey primarily on small mammals with juveniles occasionally feeding on snakes or lizards.