Environmental and intrinsic factors interact to determine energy requirements in vertebrates. Glucocorticoid hormones (GCs) are key mediators of this interaction, as they fluctuate with energetic demands and regulate physiological and behavioral responses to environmental challenges. While a great body of research has focused on GC variation among individuals, the mechanisms driving GC variation across species and at broad spatial scales remain largely unexplored. Here, we adopted a macrophysiological approach to investigate the environmental factors and life-history traits driving variation in baseline GCs across lizard species. We tested three hypotheses: (1) If GCs increase with body temperature to meet higher metabolic demand, we expect an association between average baseline GCs and the mean species’ body temperature in the field (GC-temperature dependence hypothesis); (2) If GCs mediate behavioral responses to avoid thermal extremes, we expect that individuals frequently exposed to extreme conditions exhibit higher baseline GC levels (Behavioral thermoregulation hypothesis); (3) If GCs increase to support higher energy demands in active foragers during their period of activity, we expect that active foraging species have higher baseline GCs than sit-and-wait foragers, and that GC levels increase in relation to the duration of daily activity windows (Activity hypothesis). We used biophysical models to calculate operative temperatures and the activity patterns of lizards in sun-exposed and shaded microenvironments. Then, we tested the association between baseline GCs, body temperature, operative temperatures, foraging mode, and activity windows across 37 lizard species, using data from HormoneBase. Our comparative analyses showed that variation in baseline GCs was primarily related to the mean field body temperature and foraging mode, with higher baseline GCs in active foragers with higher body temperatures. Our results suggest that body temperature and foraging mode drive GC variation through their effects on energy requirements across lizard species.