Extreme rainfall and urban flooding pose escalating risks to public health by mobilizing sewage and pathogenic microorganisms. In July 2021, record-breaking rainfall in Henan Province, China, caused catastrophic flooding, yet the microbial health risks associated with such events remain poorly quantified. Here, we applied high-throughput qPCR arrays to detect 21 pathogenic bacteria in floodwater and postflood tap water, and used quantitative microbial risk assessment (QMRA) to estimate infection probabilities for exposed residents. Our results showed that in floodwater, 21 pathogenic bacteria were detected, with Cryptosporidium spp. (579.8 gc/L) and Pseudomonas aeruginosa (13,500.9 gc/L), being prominent, which were also identified in tap water. Floodwater exposure substantially increases infection risks, highlighting ingestion and inhalation as primary pathways. Simple protective measures, such as avoiding contact with contaminated water, can significantly reduce risks. This study provides the first integrated molecular and risk-based assessment of microbial hazards during an extreme flood event. The findings underscore the importance of water quality monitoring, improved sewage and drainage management, and timely public health interventions such as boil water advisories. As climate change intensifies the frequency of extreme rainfall events, proactive surveillance and international collaboration will be essential to prevent waterborne disease outbreaks and protect vulnerable populations.