Mountain and lowland watersheds are two distinct geographical units. Understanding their hydrological processes in the context of future climate change and land use scenarios is important for watershed management. This study attempted to investigate hydrological processes and their driving factors for these two geographical units in Xitiaoxi watershed, east China, and quantify their differences through hydrological modelling. Hydrological processes in 24 mountain watersheds and 143 lowland watersheds were simulated based on a raster-based Xin’anjiang model and a Nitrogen Dynamic Polder (NDP) model, respectively. These two models were calibrated and validated with an acceptable performance (Nash-Sutcliffe efficiency coefficient of 0.81 and 0.50) in simulating discharge for mountain watersheds and water level for lowland watersheds. Based on the validated models, scenario analysis was conducted to evaluate the impacts of climate change and land use on hydrological processes. The simulation results revealed that climate change based on CMIP6 would cause a larger increase of annual runoff in the mountain watersheds than that in lowland watersheds, with the variation by 10 200% and 10 60% from 2015 to 2100 respectively. Land use change can cause a larger increase of annual runoff in lowland watersheds than that in mountain watersheds, with the variation by 3.9% and 0.6% respectively. We also found that land use change would enhance climate impacts on water balance in lowland watersheds, however, had insignificant effects in mountain watersheds. This study demonstrated that mountain and lowland watersheds are distinctly different in hydrological processes and their response to climate and land use change.