Aim: Temperature plays an important role in determining distributions of ectothermic species, yet many ectotherms have wide distributions across diverse environmental conditions. Our goal was to model regional differences in annual and seasonal activity patterns among populations of Phrynosoma platyrhinos across its climatically diverse distribution. We hypothesize that microhabitat availability and behavioural thermoregulation will not mitigate large-scale climatic differences across the species' distribution, resulting in alteration of activity patterns of populations. Location: Western deserts of North America. Taxon: Desert Horned Lizard (Phrynosoma platyrhinos). Methods: We used biophysical models to (a) model microhabitat conditions at 31 localities across the species' range, (b) model body temperature profiles of a theoretical lizard using microhabitat conditions, physiological and thermal parameters and the ability of lizards to thermoregulate behaviourally and (c) predict year-round activity patterns of P. platyrhinos across its range, quantified as the percentage of time permissible for basking or foraging. Results: The models identified that different populations of P. platyrhinos experience differences in predicted activity patterns, both daily and seasonally, with up to 67% more time suitable for foraging in the southern than northern deserts. Southern populations have more potential for year-round activity, but predicted activity is reduced during hot summer months. The northern populations have less time for activity overall because of low temperatures in the spring and fall. However, summerpredicted activity is greater than in the southern regions. Main conclusions: We detected pronounced regional differences in the times available to P. platyrhinos for activity. We conclude that behaviour and microclimate conditions are not able to fully mitigate the effects of large-scale thermal variation, and that lizards compensate for climatic variation by shifting their daily and seasonal predicted activity patterns. These differences can be tied to inter-population variation in life history traits.