The interactive effects of elevated [CO₂] and drought on leaf photosynthesis, physiology and yield in wheat (Triticum aestivum L.) are not well understood. This study evaluated the effects of persistent drought stress (35–45% of field water capacity) and elevated CO₂ (ambient concentration + 200 μmol mol^–1) on leaf photosynthesis, chlorophyll fluorescence, stress physiological indices, biomass, and grain weight (in g m⁻²) in two wheat cultivars (large-spike cultivar Z175 and multiple-spike cultivar Triumph) at the open-top chamber (OTC) experimental facility in North China. We found that elevated [CO₂] enhanced the positive effects of drought on F_v/F_m and WUE but did not ameliorate the adverse effects of drought on P_N in the two cultivars. Moreover, as a large-spike cultivar, Z175 showed enhanced photosynthesis performance and sink capacity (spike number and kernel number per spike) compared with Triumph in the grain filling stage under elevated [CO₂], which helped counteract the adverse effects of drought. In contrast, although Triumph had more tillers and spikes at the current [CO₂] concentration, most of them were thin and had limited photosynthesis capacity. The photosynthesis capacity of leaves on the main shoot and the spike number did not significantly increase in Triumph under elevated [CO₂]. Hence, elevated [CO₂] mitigated drought-induced inhibition of grain weight in Z175 plants but not in Triumph plants under persistent drought stress.