Predation plays a crucial role in community structure and population dynamics, influencing the evolution of various groups. Lizards occupy a central position in predator-prey networks, with some species engaging in saurophagy-where they act as both predator and prey. Here, we investigated saurophagy among the South American lizards, to uncover its biotic and abiotic drivers. We gathered 127 records from the literature, documenting 47 predator species from nine lizard families. Lizards of the family Tropiduridae emerged as both the most frequent predator (39.6%) and the most common prey (26%). Interspecific predation accounted for 63% of cases, while 37% involved cannibalism, primarily targeting juveniles. GLM analyses revealed a positive relationship between predator and prey size. ANOVA did not detect differences in consumption proportional to body size among lizard families. Most records (84%) were in open habitats, particularly the Caatinga and Galápagos. A structural equation model identified isothermality (β = - 0.43), evapotranspiration (β = 0.49), and longitude (β = 0.43) as significant predictors of saurophagy. A random forest model (82% accuracy) highlighted predator family, prey size, and habitat as key decision factors. This study demonstrates the frequent, non-random occurrence of saurophagy in South American lizard assemblages, contributing valuable insights into predator-prey relationships.