The Wei River catchment in the southern part of the Chinese Loess Plateau (CLP), is one of the centers of the agricultural revolution in China. The area has experienced intense land use changes since ~6000 BCE, which makes it an ideal place to study the response of fluvial systems to anthropogenic land cover change (ALCC). We applied a numerical landscape evolution model that combines the Landlab landscape evolution model with an evapotranspiration model to investigate the direct and indirect effects of ALCC on hydrological and morphological processes in the Wei River catchment since the mid-Holocene. The results show that ALCC not only leads to changes in discharge and sediment load in the catchment but also affects their sensitivity to climate change. When the proportion of agricultural land area exceeded 50% (around 1000 BCE), the sensitivities of discharge and sediment yield to climate change increased abruptly indicating a regime change in the fluvial catchment. It is associated with a large sediment pulse in the lower reaches. The model simulation results also show a link between human settlement, ALCC and floodplain development: Changes in agricultural land use changes lead to downstream sediment accumulation and floodplain development, which in turn leads to further spatial expansion of agriculture and human settlement.