In recent years, the frequent outbreaks of Ulva prolifera in the South Yellow Sea have become the largest-scale green tide disasters in the world. The causes of its outbreaks have garnered widespread attention, particularly the coupled effects of multiple factors. Leveraging the Google Earth Engine (GEE) platform, this study conducted a long-term investigation of the Yellow Sea green tide disaster and the factors using multi-source satellite imagery. Finally, the combined effects of natural environmental changes and human activities on Ulva prolifera were analyzed by redundancy analysis (RDA) and variation partitioning analysis (VPA). The results indicate: (1) Since 2018, the scale of Ulva prolifera in the South Yellow Sea has shown a distinct “biennial” trend. (2) Regarding environmental factors, SST, PAR, precipitation, and windspeed have certain effects on the growth of Ulva prolifera. However, they cannot be considered as determining factors for the outbreak of Ulva prolifera (0.002 < R2 < 0.14). Regarding anthropogenic factors, the recycle time of Pyropia yezoensis culture rafts has a relatively minor influence on the extent of Ulva prolifera. There exists a certain positive correlation (R2 = 0.45) between the human footprint index (HFI) of Jiangsu Province and the annual variation in Ulva prolifera area in the South Yellow Sea. (3) The combined effects of multiple factors influence green tide outbreaks. The Ulvatotal explanatory power of SST, PAR, precipitation, windspeed, HFI, and the recycle time of Pyropia yezoensis culture rafts for the annual variation in the Ulva prolifera area is 31.8%, with these factors interweaving and mutually influencing each other. This study offers important insights into quantifying the driving forces behind Ulva prolifera in the South Yellow Sea, providing valuable information for a deeper comprehension of the complexity of marine ecosystems and sustainable management.