Behavioral thermoregulation is an efficient mechanism to buffer the physiological effects of climate change. Thermal ecology studies have traditionally tested how thermal constraints shape thermoregulatory behaviors without accounting for the potential major effects of landscape structure and water availability. Thus, we lack a general understanding of the multifactorial determinants of thermoregulatory behaviors in natural populations. In this study, we quantified the relative contribution of elevation, thermal gradient, moisture gradient, and landscape structure in explaining geographic variation in thermoregulation strategies of a terrestrial ectotherm species. We measured field-active body temperature, thermal preferences, and operative environmental temperatures to calculate thermoregulation indices, including thermal quality of the habitat and thermoregulation efficiency for a very large sample of common lizards (Zootoca vivipara) from 21 populations over 3 yr across the Massif Central mountain range in France. We used an information-theoretic approach to compare eight a priori thermo-hydroregulation hypotheses predicting how behavioral thermoregulation should respond to environmental conditions. Environmental characteristics exerted little influence on thermal preference with the exception that females from habitats with permanent access to water had lower thermal preferences. Field body temperatures and accuracy of thermoregulation were best predicted by the interaction between air temperature and a moisture index. In mesic environments, field body temperature and thermoregulation accuracy increased with air temperature, but they decreased in drier habitats. Thermoregulation efficiency (difference between thermoregulation inaccuracy and the thermal quality of the habitat) was maximized in cooler and more humid environments and was mostly influenced by the thermal quality of the habitat. Our study highlights complex patterns of variation in thermoregulation strategies, which are mostly explained by the interaction between temperature and water availability, independent of the elevation gradient or thermal heterogeneity. Although changes in landscape structure were expected to be the main driver of extinction rate of temperate zone ectotherms with ongoing global change, we conclude that changes in water availability coupled with rising temperatures might have a drastic impact on the population dynamics of some ectotherm species.