The effectiveness of urban hydrological processes in mitigating the urban heat island (UHI) effect and human thermal stress in the megacity of Nanjing during an extreme heat wave event (6th-10th August 2013) was assessed using Weather Research and Forecasting Single-Layer Urban Canopy Models. The inclusion of urban hydrological processes improved model performance, with more reasonable diurnal cycles and smaller mean errors, root mean square errors, and normalized root mean square errors for meteorological variables. Through evaporative cooling, urban hydrological processes can greatly increase specific and relative humidity, while reducing near-surface and surface temperatures, wind speed, and planetary boundary layer (PBL) height, and the cooling and wetting effects could affect the entire PBL, especially in low-intensity residential areas. Urban hydrological processes can effectively mitigate both the near-surface and surface UHI effect. The city-wide mitigation effectiveness of near-surface UHI ranged between 0.9 degrees C and 1.1 degrees C throughout the day, while the city-wide mitigation effectiveness of surface UHI at noon reached similar to 5 degrees C. The maximum reduction of near-surface and surface UHI in low-intensity residential areas reached 1.3 degrees C and 10.0 degrees C, respectively. Changes in heat stress indices indicate that the cooling effect improves human thermal comfort at night, while the increased humidity outweighs the cooling effect and exacerbates human thermal discomfort during daytime. The city-wide thermal stress increased by up to 0.4 degrees C, 0.2 degrees C, and 0.5 degrees C during daytime and decreased by up to 0.4 degrees C, 0.3 degrees C, and 0.6 degrees C at night for wet-bulb globe temperature, apparent temperature, and humidity index, respectively.