Rising temperature from climate change is the most threatening factor worldwide for crop production. Sustainable wheat production is a challenge due to climate change and variability, which is ultimately a serious threat to food security in Pakistan. A series of field experiments were conducted during seasons 2013–2014 and 2014–2015 in the semi-arid (Faisalabad) and arid (Layyah) regions of Punjab-Pakistan. Three spring wheat genotypes were evaluated under eleven sowing dates from 16 October to 16 March, with an interval of 14–16 days in the two regions. Data for the model calibration and evaluation were collected from field experiments following the standard procedures and protocols. The grain yield under future climate scenarios was simulated by using a well-calibrated CERES-wheat model included in DSSAT v4.7. Future (2051–2100) and baseline (1980–2015) climatic data were simulated using 29 global circulation models (GCMs) under representative concentration pathway (RCP) 8.5. These GCMs were distributed among five quadrants of climatic conditions (Hot/Wet, Hot/Dry, Cool/Dry, Cool/Wet, and Middle) by a stretched distribution approach based on temperature and rainfall change. A maximum of ten GCMs predicted the chances of Middle climatic conditions during the second half of the century (2051–2100). The average temperature during the wheat season in a semi-arid region and arid region would increase by 3.52 °C and 3.84 °C, respectively, under Middle climatic conditions using the RCP 8.5 scenario during the second half-century. The simulated grain yield was reduced by 23.5% in the semi-arid region and 35.45% in the arid region under Middle climatic conditions (scenario). Mean seasonal temperature (MST) of sowing dates ranged from 16 to 27.3 °C, while the mean temperature from the heading to maturity (MTHM) stage was varying between 12.9 to 30.4 °C. Coefficients of determination (R2) between wheat morphology parameters and temperature were highly significant, with a range of 0.84–0.96. Impacts of temperature on wheat sown on 15 March were found to be as severe as to exterminate the crop before heading. The spikes and spikelets were not formed under a mean seasonal temperature higher than 25.5 °C. In a nutshell, elevated temperature (3–4 °C) till the end-century can reduce grain yield by about 30% in semi-arid and arid regions of Pakistan. These findings are crucial for growers and especially for policymakers to decide on sustainable wheat production for food security in the region.