The drought- and thermo-tolerant Quercus pubescens, a tree species growing on both acidic and calcareous soils in the sub-Mediterranean region, was exposed to soil drought (−60% to −80% soil water content) and air warming (+1.2 °C daytime temperature), singly and in combination. The experiment was conducted on two natural forest soils with similar texture but different pH (acidic and calcareous soils). The physiological (photosynthesis) and biochemical (antioxidant system) responses of Q. pubescens were investigated. On acidic soil, Q. pubescens had a higher reactive oxygen species (ROS) content than on calcareous soil, confirming that this species is better adapted to the latter soil type. A down-regulation of ascorbate-glutathione cycle enzymes suggests that ROS were used as signalling molecules. Air warming stimulated stomatal opening, while soil drought induced stomatal closure in the late afternoon and reduced Rubisco carboxylation efficiency. Photosynthetic performance in the combined treatment was higher than under single drought stress and similar to control and air warming. Q. pubescens biochemical responses depended on soil pH. On acidic soil, Q. pubescens trees exposed to air warming used ROS as signalling molecules. On calcareous soil, these trees were able to balance both soil drought and air warming stress, avoiding ROS toxic effects by increasing antioxidant enzyme activitiy and maintaining a high enzymatic antioxidant defence. When combined, drought and air warming induced either more severe (higher oxidative pressure and impairment of the light-harvesting complex) or different responses (decline of the thermal energy dissipation capacity) relative to the single stressors. Overall, however, Q. pubescens preserved the functionality of the photosynthetic apparatus and controlled the antioxidant system response, thus confirming its drought and thermo-tolerance and therefore its potential to adapt to the ongoing climate change.