Machine learning algorithms are becoming more and more popular in natural disaster assessment. Although the technology has been tested in flood susceptibility analysis of several watersheds, research on global flood disaster risk assessment based on machine learning methods is still rare. Considering that the watershed is the basic unit of water management, the purpose of this study was to conduct a risk assessment of floods in the global fourth-level watersheds. Thirteen conditioning factors were selected, including: maximum daily precipitation, precipitation concentration degree, altitude, slope, relief degree of land surface, soil type, Manning coefficient, proportion of forest and shrubland, proportion of artificial surface, proportion of cropland, drainage density, population, and gross domestic product. Four machine learning algorithms were selected in this study: logistic regression, naive Bayes, AdaBoost, and random forest. The global susceptibility assessment model was constructed based on four machine learning algorithms, thirteen conditioning factors, and global flood inventories. The evaluation results of the model show that the random forest performed better in the test, and is an efficient and reliable tool in flood susceptibility assessment. Sensitivity analysis of the conditioning factors showed that precipitation concentration degree and Manning coefficient were the main factors affecting flood risk in the watersheds. The susceptibility map showed that fourth-level watersheds in the global high-risk area accounted for a large proportion of the total watersheds. With the increase of extreme hydrological events caused by climate change, global flood disasters are still one of the most threatening natural disasters. The global flood susceptibility map from this study can provide a reference for global flood management.