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Background: Diarrhea remains a common infectious disease caused by various risk factors in developing countries. This study investigated the incidence rate and temporal associations between diarrhea and meteorological determinants in five regions of Surabaya, Indonesia. Method: Monthly diarrhea records from local governmental health facilities in Surabaya and monthly means of weather variables, including average temperature, precipitation, and relative humidity from Meteorology, Climatology, and Geophysical Agency were collected from January 2018 to September 2020. The generalized additive model was employed to quantify the time lag association between diarrhea risk and extremely low (5th percentile) and high (95th percentile) monthly weather variations in the north, central, west, south, and east regions of Surabaya (lag of 0–2 months). Result: The average incidence rate for diarrhea was 11.4 per 100,000 during the study period, with a higher incidence during rainy season (November to March) and in East Surabaya. This study showed that the weather condition with the lowest diarrhea risks varied with the region. The diarrhea risks were associated with extremely low and high temperatures, with the highest RR of 5.39 (95% CI 4.61, 6.17) in the east region, with 1 month of lag time following the extreme temperatures. Extremely low relative humidity increased the diarrhea risks in some regions of Surabaya, with the highest risk in the west region at lag 0 (RR = 2.13 (95% CI 1.79, 2.47)). Extremely high precipitation significantly affects the risk of diarrhea in the central region, at 0 months of lag time, with an RR of 3.05 (95% CI 2.09, 4.01). Conclusion: This study identified a high incidence of diarrhea in the rainy season and in the deficient developed regions of Surabaya, providing evidence that weather magnifies the adverse effects of inadequate environmental sanitation. This study suggests the local environmental and health sectors codevelop a weather-based early warning system and improve local sanitation practices as prevention measures in response to increasing risks of infectious diseases.