Remarkable warm‒wet climate shifts and intensive cropland expansion strongly affected carbon (C) cycle and threaten agricultural sustainability in northwest China. In this study, we integrated a process-based ecosystem model and an empirical C bookkeeping model to investigate the coupled and isolated effects of arable land conversions and climate change (CLM) on regional C balance in a typical watershed of northwest China. Results revealed that the farmland area increased by 3367.31 km² during 1979–2014. The combined effects of CLM with net cropland expansion enlarged the vegetation C (VEGC) and the soil organic C (SOC) stock by 2.83 and 11.83 Tg, respectively, and were strongest in 2008–2014. The conversions between desert grassland and cropland were the major driving forces for regional C balance. Cropland expansion shared equal effects on VEGC increase with CLM, but its effect on SOC increment was 53 times larger than CLM’s. VEGC was more responsive to CLM, whereas SOC gained more benefits from land management. The C sink from reclamation suffered from high water consumption and is facing great threats due to glaciers and mountain lake shrinking and groundwater overpumping. Water-saving irrigation techniques and environmentally friendly water use strategies are essential for local agricultural sustainability.