Climate change poses a challenge for resource utilization and environmental pollution issues caused by agricultural production, especially in arid to semi-arid regions. Farmland water, carbon and nitrogen balances are closely related to these resource and environmental issues. Thus, the Agro-Hydrological & chemical and Crop systems simulator was used to assess the response of water, carbon and nitrogen balances to climate change in a spring wheat farmland of arid to semi-arid Northwest China and to propose adaptation strategies. Five Global Climate Models from the Coupled Model Intercomparison Project 6 and two Shared Socioeconomic Pathways (SSP1–2.6 and SSP5–8.5) were used to establish scenarios with the Agro-Hydrological & chemical and Crop systems simulator to simulate farmland water, carbon and nitrogen balances for the 2025–2100 period. Various irrigation amounts and nitrogen fertilization rates were tested as compensation strategies. Results indicated that climate change could negatively affect farmland water, carbon and nitrogen balances, especially under the SSP5–8.5 scenario. Precipitation showed an increasing trend, thus percolation increased and soil water consumption decreased from 2025 to 2100. However, for the carbon budget, although the soil carbon dioxide emissions tend to decrease, the net primary production was also significantly reduced, which resulted in declining the net ecosystem carbon budget under future climatic conditions. In addition, higher temperature and increased precipitation enhanced soil inorganic nitrogen leaching and nitrous oxide emissions but reduced ammonia volatilization from 2025 to 2100. Overall, the soil total nitrogen loss was increased over time, whereas crop nitrogen uptake was significantly reduced. In relation to the SSP1–2.6 scenario, the SSP5–8.5 scenario accelerated the increase rates of soil water percolation and total nitrogen loss over time, as well as the decrease rates of crop nitrogen uptake and net primary production over time. The negative effects caused by climate change can be mitigated by reducing irrigation and increasing nitrogen fertilization. For the SSP1–2.6 scenario, 30% irrigation reduction and 30% nitrogen fertilization increase can effectively decrease soil water percolation and the related nitrogen losses while crop nitrogen uptake, net primary production and net ecosystem carbon budget increase in relation to the current management (irrigation = 240 mm and nitrogen fertilization = 200 kg ha–1). For SSP5–8.5 the strategy with 45% irrigation reduction and 45% nitrogen fertilization increase can also decrease nitrogen losses and increase crop nitrogen uptake, net primary production and net ecosystem carbon budget.