Climate change is the most devastating issue of 21st century especially for agricultural production and will be more severe in the future. South Asian countries including Pakistan are the most vulnerable to climate change. Climate change deals with future issues. The use of general circulation models (GCMs) and crop simulation models provides a scientific approach to study the impact of climate change on agricultural production and world food security. Field experiments were conducted from 1st March to 15th May with 15 days interval at three locations Faisalabad, Multan and Bahawalpur during two growing seasons (2013 and 2014) consecutively. Different statistical approaches were used to analyze the data. Cultivar MNH-886 and CIM-598 sown 1st April to 1st May produced significantly higher seed yield in all locations. Higher net monetary return was produced when sown on the 15th of April. The CSM-CROPGRO-COTTON was parameterized with field data. The model performed reasonably for phenology, growth, seed yield and yield components among locations and years. Studies on future climate based on RCP 4.5 and RCP 8.5 using an ensemble of Global Circulation Models report that the seasonal average temperature in the region would raise 1.52ºC and 2.60ºC in the near term (2010-2039) and mid-century (2040-2069), respectively. Our simulated results using future climate based on such RCPs indicate that mean seed yield would decrease by 8% and 20% in RCP 4.5 scenario, while 10% and 30% reduction would be expected in RCP 8.5 scenario in the near term (2010-2039) and mid-century (2040-2069), respectively compared with the baseline (1980-2010). Our simulations also indicated that cultivar MNH-886 and CIM-598 would have lower yield reduction under those future climate scenarios; hence the characteristics of these cultivars could be used as baseline for the development of climate resilient germplasm. Last but not least our simulations indicate that sowing as early as 20 days as compared to current sowing date (15th April) as an adaptation technology. Moreover, 18% and 29% increase in plant density for spreading and erect type cultivars, 25% increase in nitrogen amount, 30% reduction in irrigation and 15% upsurge in genetic potential would reduce the negative impact of temperature and rainfall variability in mid-century climate (2040-2069).