The assessment of climate extremes’ impact on crop yield is essential to improve our understanding of agricultural resilience. In the present study, we analyzed the potential impact of climate extremes on wheat and cotton production in Southern Punjab, Pakistan using 30-year observed data from the Pakistan Meteorological Department (PMD) and the fifth-generation reanalysis data (ERA-5) from the European Center for Medium-Range Weather Forecasts (ECMWF). Cotton is a Kharif season crop that is sown in May and harvested in October, and wheat is a Rabi season crop that is planted in November and harvested in April. The agricultural data (1985–2015) that contained the crop area and crop yield were obtained from the Bureau of Statistics, Punjab for six selected districts in Southern Punjab. Three precipitation indices, namely consecutive dry days (CDD), consecutive wet days (CWD) and total precipitation of wet days (PRCPTOT), and four temperature indices, namely warm days (TX90p), warm nights (TN90p), cool days (TX10p) and cool nights (TN10p), were selected to analyze the potential impacts of climate extremes on crop production. (1) We found a potential association of TX10p, TN10p, TX90p and TN90p with crop yield in those years for which the production area remained the same. (2) In a few districts of the study area, the wheat yield losses in the Rabi season were associated with an increase in warmer days and warmer nights. (3) The grain size was suppressed due to an increase in the frequency of TX90p and TN90p, which ultimately reduced the net crop production. (4) In some districts, we found strong positive correlations between extreme temperature indices and crop yield; however, other potential factors such as the use of advanced technology, fertilizer, seeds, etc., may lead to improved net production. This study can help in adaptation planning for resilient agricultural production under the stress of climate extreme events in Southern Punjab.