Climate change has caused significant impacts on water resource redistribution around the world and posed a great threat in the last several decades due to intensive human activities. The impacts of human water use and management on regional water resources remain unclear as they are intertwined with the impacts of climate change. In this study, we disentangled the impact of climate-induced human activities on groundwater resources in a typical region of the semi-arid North China Plain based on a process-oriented groundwater modelling approach accounting for climate-human-groundwater interactions. We found that the climate-induced human effect is amplified in water resources management (‘amplifying effect’) for our study region under future climate scenarios. We specifically derived a tipping point for annual precipitation of 350 mm, below which the climate-induced human activities on groundwater withdrawal will cause significant ‘amplifying effect’ on groundwater depletion. Furthermore, we explored the different pumping scenarios under various climate conditions and investigated the pumping thresholds, which the pumping amount should not exceed (4 × 10⁷ m³) in order to control future groundwater level depletion. Our results highlight that it is critical to implement adaptive water use practices, such as water-saving irrigation technologies in the semi-arid regions, in order to mitigate the negative impacts of groundwater overexploitation, particularly when annual precipitation is anomalously low.