AbstractFloods are widespread and dangerous natural hazards worldwide. It is essential to grasp the causes of floods to mitigate their severe effects on people and society. The key drivers of flood susceptibility in rapidly urbanizing areas can vary depending on the specific context and require further investigation. This research developed an index system comprising 10 indicators associated with factors and environments that lead to disasters, and used machine learning methods to assess flood susceptibility. The core urban area of the Yangtze River Delta served as a case study. Four scenarios depicting separate and combined effects of climate change and human activity were evaluated using data from various periods, to measure the spatial variability in flood susceptibility. The findings demonstrate that the extreme gradient boosting model outperformed the decision tree, support vector machine, and stacked models in evaluating flood susceptibility. Both climate change and human activity were found to act as catalysts for flooding in the region. Areas with increasing susceptibility were mainly distributed to the northwest and southeast of Taihu Lake. Areas with increased flood susceptibility caused by climate change were significantly larger than those caused by human activity, indicating that climate change was the dominant factor influencing flood susceptibility in the region. By comparing the relationship between the indicators and flood susceptibility, the rising intensity and frequency of extreme precipitation as well as an increase in impervious surface areas were identified as important reasons of heightened flood susceptibility in the Yangtze River Delta region. This study emphasized the significance of formulating adaptive strategies to enhance flood control capabilities to cope with the changing environment.