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Designing the adaptation strategies by studying biochemical, physiological and agronomic response of wheat to climate change will be important for ensuring yield stability and economic sustainability in future. The current study was conducted under three variable climatic sites of rainfed field Pothwar viz. Islamabad (Optimum climatic conditions), URF-Koont Chakwal (Moderate temperature and water stress) and Talagang (high temperature and water stress) under four sowing dates (SD1 = 21-30 Oct, SD2 = 11-20 Nov, SD3 = 01-10 Dec, and SD4 = 21-30 Dec during 2013-14 and 2014-15) and five wheat genotypes. The study quantified the biochemical, physiological and agronomic response of wheat under different treatments. Stress in the form of drought and unfavorable temperature resulted in increase of total soluble sugar content (TSSC), total soluble protein content (TSPC) proline and leaf membrane stability index (LMSI), while decrease in relative water content (RWC), leaf area (LA), plant height (PH), biological yield (BY) and grain yield (GY). Leaf gaseous exchange parameters i.e. net photosynthesis (A(n)), intercellular CO2 concentration (C-i), transpiration rate (Tr) and stomatal conductance (g(s)) remained highest under optimum conditions as compared to stress while opposite trend was observed for stomatal resistance (r(s)). Correlation analysis among biochemical, physiological and agronomic traits showed that grain yield was positively correlated with RWC, LA, A(n), C-i, E, g(s), SPAD, PH and BY while negatively correlated with all other parameters. These results suggested to change sowing dates based on prevailing climatic conditions and use of tolerant cultivar to have higher sustainable crop productivity.