Grain yields in wheat can be limited by the assimilate supply (source) or by the carbohydrate demand of the grains (sink). Recently, there have been questions regarding the capability of crop models to simulate the physiology of source-sink interactions in crops; however, crop models scarcely tested with source-sink partitioning. DSSAT_CERES_Wheat model was used with details of field experimental data having treatments of manipulated source (i.e., assimilate supply), sink (i.e., kernel number). The aim of the present study was to assess the impact of different levels of nitrogen and source-sink manipulation on wheat crop and to model source-sink partitioning in wheat under varying N-Regimes and climatic conditions. The experiment was conducted during wheat growing seasons of 2015–16 and 2016–17, at two locations (Islamabad and URF Koont Chakwal), under five different levels of nitrogen and three source sink treatments (Control (100 % RUE), 50 % shading pre-anthesis (50 % RUE), 50 % spike removal i.e. spike halving) using randomized complete block design. Recommended rates of fertilizer were applied with the exception of nitrogen which was 0, 50, 100, 150 and 200 kg ha−1, while each treatment was replicated thrice. CERES-Wheat model was calibrated using 2015–16 observed data while model was evaluated using two-year field collected data of two sites i.e. Islamabad and Chakwal. The model was able to simulate treatments impacts on phenology (R2, RMSE and d-index values of 0.89, 2.80 days and 0.97 respectively at Islamabad while at Chakwal R2 = 0.89, RMSE = 2.65 days and d-index = 0.94), leaf area index (R2 = 0.94, 0.94, RMSE = 0.51, 0.38 and d-index = 0.98 and 0.92 at Islamabad and Chakwal respectively), biomass (R2 = 0.98, 0.96, RMSE = 370, 450 kg ha−1 and d-index = 0.96 and 0.95 at Islamabad and Chakwal respectively), grain yield (R2 = 0.97,0.96, RMSE = 0.17, 0.2 t ha−1, and d-index = 0.95 and 0.93 at Islamabad and Chakwal respectively), harvest index, soil nitrogen, crop nitrogen and grain nitrogen with good accuracy. The observed range for biomass water use efficiency (BM_WUE) was 34.1–14.5 kg ha−1 mm−1 while grain WUE remained in the range of 10.3–3.7 kg ha−1 mm−1. The results depicted that model could reproduce observed effects of shading and halving the spikes. Crop response to modified radiation use efficiency (RUE) was variable among sites which could be critical for studying crop environment interactions, improving WUE, estimating genetically and atmospheric CO2-related increased RUE, analyzing impact of solar dimming and source manipulations under biotic stress.