Climate change has made weather patterns less predictable, making situations more challenging for farmers throughout the production process. This study investigates the impact of climatic variables (maximum and minimum temperature, rainfall, humidity at 8 AM and 5 PM) and fertilizer application on wheat production in Bahawalnagar district, a major wheat producing region of Punjab, Pakistan. The study utilizes the Mann–Kendall and multiple linear regression analysis to check climatic trends and identify the factors influencing wheat yield from 1991 to 2022. The study utilized a regression model to compare actual and predicted wheat yields. The results showed a decreasing trend in rainfall and an increasing trend in both maximum and minimum temperatures during the wheat growing season. Sen’s slope values for maximum temperature (0.037), minimum temperature (0.007), humidity at 8 AM (0.275), and humidity at 5 PM (0.167) indicate the direction and magnitude of trends. The regression model explained about 92% of the variance in the wheat yield. The regression analysis of humidity at both 8 AM (p = 0.001) and 5 PM (p = 0.001) shows a significant positive correlation with wheat yield. Fertilizer use exhibited a significant positive association with wheat yield (β = 9.58). Fertilizer application for wheat crops increased from 112.4 kg/ha in 1991 to 284.3 kg/ha in 2021. The regression model identifies that the average wheat yield loss from 1991 to 2022 is approximately 0.1208 t/ha per year because of the influence of climatic factors. The study findings underscore the importance of the utilization of adaptive agricultural practices that can ensure food security and improve agricultural sustainability in the region.