AbstractIntensified human activities have been seriously threatening the structure and ecological processes of ecosystems, resulting in habitat degradation. Therefore, coordinating the coupling between human activities and habitat quality (HQ) is crucial for high‐quality sustainable regional development and human well‐being. This study evaluated the human activities and HQ in the Pearl River Delta (PRD) urban agglomeration in China from 2000 to 2020 using the human footprint index (HFI) and the integrated valuation of ecosystem services and tradeoffs model. Then, we employed bivariate spatial autocorrelation and a coupling coordination degree (CCD) model to explore the synergistic relationship between human activities and HQ. The results show that spatial changes in HQ were predominantly driven by human activities. The gradual outward urban expansion resulted in significant HQ degradation. Slight HQ improvement by ecological restoration in urban outskirts cannot offset HQ losses caused by urbanization. During the study period, high‐HQ low‐HFI clusters decreased by 1.02%, while low‐HQ high‐HFI clusters increased by 4.67%, the two main clustering types in the PRD. Despite the CCD between HFI and HQ increased after 2010, the continuous changes of CCD characteristics from the HFI significantly lagged type to the HQ lagged. HFI showed an inverted U‐shaped relationship with CCD. The CCD peaks during 2000–2020 corresponded to HFI decreasing from 0.711 to 0.566. This indicates that the risk of decoupling between human activities and HQ gradually increased. Furthermore, CCD levels and characteristics in different bivariate clusters exhibited varying changes over time. These results reveal that the spatiotemporal dislocation between urbanization and ecological restoration induced the spatial nonstationarity of the coupling relationship between human activities and HQ. Urbanization exacerbates the imbalance between human development and biodiversity conservation. Therefore, we suggest reasonably delimiting urban boundaries, controlling the scale of urban sprawl, and strengthening biodiversity protection in areas undergoing rapid urbanization. In addition, we advocate for the division of ecological barrier zones, urban development buffer zones, and urban built‐up areas, each with tailored management and protection measures. Our findings can provide an important reference for the ecological restoration of urban agglomerations.