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Cotton (Gossypium hirsutumL.)—wheat (Triticum aestivum(L.) emend Fiori & Paol) cropping system with conservation agriculture (CA) practices is being recommended for diversification of the rice (Oryza sativaL.)—wheat (RW) system in South Asia including Indo-Gangetic Plains (IGP). But, long-term studies are limited on the impacts of CA-based management including nitrogen (N) fertilization for cotton–wheat (hereafter mentioned as CW) system to assess crop yield sustainability and soil health. Therefore, in this study of seven years (2013–14 to 2019–20), conventional tillage (CT) was compared with zero-till (ZT) permanent narrow (PNB), broad (PBB), and flat (PFB) beds with and without residue (R) and 100%N (in all treatments/plots) and 75%N (imposed only on residue-added plots after 3 years) in the alluvial soils of IGP. Mean cotton yield in ZT permanent broad (PBB100N + R) and flat (PFB100N + R) bed with residue and 100%N were higher by 52 and 53%, respectively, than with CT. The same permanent broad bed with residue but 75%N (PBB75N + R) increased 49% mean cotton yield than CT. Similarly, PBB100N + R, PFB100N + R, and PBB75N + R yielded more wheat by 16, 17, and 15%, respectively (P< 0.05) than CT. Again, PBB100N + R, PBB75N + R and PFB100N + R had significantly higher sustainable yield indices of cotton (30–33%), wheat (16–18%), and CW system (28–31%) than CT. PBB100N + R had 27.5% higher total organic carbon stock and 56% higher system water productivity and conserved highest 173.2 mm water annually compared to CT (P< 0.05). Notably, PBB75N + R could save 472.5 kg N ha−1from application in 7 years and reduce GWP by 6.2% in CW system compared to CT (P< 0.05). A 25% N saving under PBB75N + R without compromising crop productivity and reduction in global warming potential (GWP) may be a strategy for sustainability of the CW rotation. Thus, the CW rotation with CA-based PBB100N + R and PBB75N + R may be adopted in the IGP of India with higher crop and water productivity, profitability, carbon stock and lower GWP.