Human activities and climate change pose severe challenges to global water, food, and ecosystem security. However, it remains unclear whether the farmland water-food-ecology (WFE) system can maintain stable and sustainable development under these pressures. This study integrated an agro-hydrological model (AHC), human activity scenarios, and global climate models to evaluate the impacts of human activities and climate change the sustainability and stability of the WFE system in wheat farmlands of arid Northwest China, and to explore potential adaptation pathways. Scenarios were simulated using the AHC model, which incorporated 132 human water-saving and nitrogen-reduction practices, as well as two Shared Socioeconomic Pathways (SSP1-2.6 and SSP5-8.5) from CMIP6 for the period 2025-2100. These simulations projected water use efficiency (WUE), crop yield, biomass, farmland ecosystem service value (FESV), and the sustainability and stability indexes of the integrated WFE system under different scenarios. Results showed that moderate water-saving and nitrogen reduction practices (irrigation of 150-270 mm and nitrogen input of 160-280 kg ha(-1)) enhanced the farmland WFE system sustainability by increasing yield, biomass, WUE, and positive FESV while reducing negative FESV. Such management accounts for 20-26% of the simulated scenarios that improved sustainability by 10-22% while maintaining high productivity. Moreover, climate change under SSP5-8.5 markedly reduced system stability, with decadal declines of 0.02 kg m(-3) in WUE, 180 kg ha(-1) in yield, 480 kg ha(-1) in biomass, and 580 CNY ha(-1) total FESV, which were 8-14.5 times greater than those under SSP1-2.6. These declines caused 67-82% ductions in WFE system stability from the near-term (2025-2050) to the long-term (2025-2100). Notably, strategy combining a 45% reduction in current irrigation (240 mm) with a 45% increase in current nitrogen application (200 kg ha(-1)) improved all WFE assessment indicators, enhancing system stability by 19-86% under SSP5-8.5. This study provides insights for maintaining the stability and sustainable development of agroecosystems in arid regions under intensified human activities and climate change.