The improvement in the agricultural production through continuous and heavy nutrient input like nitrogen fertilizer under the upland red soil of south China deteriorates soil quality, and this practice in the future could threaten future food production and cause serious environmental problems in China. This research is initiated with the objectives of evaluating the impacts of long-term chemical nitrogen fertilization on soil quality, crop yield, and greenhouse gas emissions, with insights into post-lime application responses. Compared to sole application of chemical nitrogen fertilization, combined application with lime increased soil indicators (pH by 6.30 %–7.76 %, Ca2+ by 90.06 %–252.77 %, Mg2+ by 184.47 %–358.05 %, available P by 5.05 %–30.04 %, and soil alkali hydrolysable N by 23.49 %–41.55 %. Combined application of chemical nitrogen fertilization with lime (NPCa (0.59), NPKCa (0.61), and NKCa (0.27) significantly improved soil quality index compared to the sole application of chemical nitrogen fertilization (NP (0.31), NPK (0.36), and NK (0.16). Compared to sole application of chemical nitrogen fertilization, combined application with lime increased grain yield by 48.36 %–61.49 %. Structural equation modeling elucidated that combined application of chemical nitrogen fertilization and lime improved wheat grain yield by improving soil quality. Exchangeable Ca2+, exchangeable Mg2+, pH, and exchangeable Al3+ were the most influential factors of wheat grain yield. Overall, the combined application of chemical nitrogen fertilization and lime decreased global warming potential (calculated from N2O and CO2) by 16.92 % emissions compared to the sole application of chemical nitrogen fertilization. Therefore, liming acidic soil in upland red soil of South China is a promising management option for improved soil quality, wheat grain yield, and mitigation of greenhouse gas emissions. Display omitted •Long-term chemical nitrogen fertilization (CNF) reduced soil quality.•Combining the application of CNF and lime enhanced the soil quality of the sole CNF.•pH, Ca2+, Mg2+, AvP, and alkali hydrolysable N were determinants of soil quality.•Combined application of CNF with lime improved wheat yield compared to sole CNF.•Combining CNF with lime decreased global warming potential compared to sole CNF.