Climate change has emerged as one of the most significant challenges in modern agriculture, with potential implications for global food security. The impact of changing climatic conditions on crop yield, particularly for staple crops like wheat, has raised concerns about future food production. By integrating historical climate data, GCM (CMIP3) projections, and wheat-yield records, our analysis aims to provide significant insights into how climate change may affect wheat output. This research uses advanced machine learning models to explore the intricate relationship between climate change and wheat-yield prediction. Machine learning models used include multiple linear regression (MLR), boosted tree, random forest, ensemble models, and several types of ANNs: ANN (multi-layer perceptron), ANN (probabilistic neural network), ANN (generalized feed-forward), and ANN (linear regression). The model was evaluated and validated against yield and weather data from three Punjab, Pakistan, regions (1991–2021). The calibrated yield response model used downscaled global climate model (GCM) outputs for the SRA2, B1, and A1B average collective CO2 emissions scenarios to anticipate yield changes through 2052. Results showed that maximum temperature (R = 0.116) was the primary climate factor affecting wheat yield in Punjab, preceding the Tmin (R = 0.114), while rainfall had a negligible impact (R = 0.000). The ensemble model (R = 0.988, nRMSE= 8.0%, MAE = 0.090) demonstrated outstanding yield performance, outperforming Random Forest Regression (R = 0.909, nRMSE = 18%, MAE = 0.182), ANN(MLP) (R = 0.902, MAE = 0.238, nRMSE = 17.0%), and boosting tree (R = 0.902, nRMSE = 20%, MAE = 0.198). ANN(PNN) performed inadequately. The ensemble model and RF showed better yield results with R2 = 0.953, 0.791. The expected yield is 5.5% lower than the greatest average yield reported at the site in 2052. The study predicts that site-specific wheat output will experience a significant loss due to climate change. This decrease, which is anticipated to be 5.5% lower than the highest yield ever recorded, points to a potential future loss in wheat output that might worsen food insecurity. Additionally, our findings highlighted that ensemble approaches leveraging multiple model strengths could offer more accurate and reliable predictions under varying climate scenarios. This suggests a significant potential for integrating machine learning in developing climate-resilient agricultural practices, paving the way for future sustainable food security solutions.