Extreme climatic events, such as heat waves, cold snaps and drought spells, related to global climate change, have become more frequent and intense in recent years. Acclimation of plant physiological processes to changes in environmental conditions is a key component of plant adaptation to climate change. We assessed the temperature response of leaf photosynthetic parameters in wheat grown under contrasting water regimes and growth temperatures (Tgrowth). Two independent experiments were conducted under controlled conditions. In Experiment 1, two wheat genotypes were subjected to well-watered or drought-stressed treatments; in Experiment 2, the two water regimes combined with high, medium and low Tgrowth were imposed on one genotype. Parameters of a biochemical C3-photosynthesis model were estimated at six leaf temperatures for each factor combination. Photosynthesis acclimated more to drought than to Tgrowth. Drought affected photosynthesis by lowering its optimum temperature (Topt) and the values at Topt of light-saturated net photosynthesis, stomatal conductance, mesophyll conductance, the maximum rate of electron transport (Jmax) and the maximum rate of carboxylation by Rubisco (Vcmax). Topt for Vcmax was up to 40°C under well-watered conditions but 24–34°C under drought. The decrease in photosynthesis under drought varied among Tgrowth but was similar between genotypes. The temperature response of photosynthetic quantum yield under drought was partly attributed to photorespiration but more to alternative electron transport. All these changes in biochemical parameters could not be fully explained by the changed leaf nitrogen content. Further model analysis showed that both diffusional and biochemical parameters of photosynthesis and their thermal sensitivity acclimate little to Tgrowth, but acclimate considerably to drought and the combination of drought and Tgrowth. The commonly used modelling approaches, which typically consider the response of diffusional parameters, but ignore acclimation responses of biochemical parameters to drought and Tgrowth, strongly overestimate leaf photosynthesis under variable temperature and drought.