The rainfall anomaly (RA) associated with El Niño-Southern Oscillation (ENSO) has various unwanted impacts on agricultural system globally. The loss of inorganic nitrogen (N) depending on extreme wet or dry conditions is a major concern. The main objective of this study was to adapt site-specific N strategies to mitigate the effects of ENSO on yields of winter wheat (Triticum aestivum L.; WW) system. After thorough calibration and evaluation, Decision Support Systems for Agrotechnology Transfer (DSSAT, version 4.5) model suite was adapted. Seasonal analysis was used to compare the variability in simulated leached-N, N uptake, and WW yields under long-term historical real-weather conditions. The site X climate interactions and impacts of weather factors on WW yields were assessed across 60 growing seasons in three phases of ENSO: El Niño (EN), La Niña (LN), and neutral (NT). Based on RA, the simulated yields were lower during LN than EN (11 %) and NT (12 %) on coastal sandy-loam soils and higher during LN than EN (13 %) and NT (8 %) on heavy silt loam soils at valley. N strategy with basal of 22 kg N ha−1 + a split of 112 kg N ha−1 at Feekes (F) 4 stage of WW was adapted for maximum yield and minimum N leaching during LN at valley and NT at coastal sites. However, basal of 22 kg N ha−1 + two equal splits of 56 kg N ha−1 at both F4 and F6 was found as the most adaptable N strategy during both EN and NT phases at valley and EN and LN at coastal sites.