Diarrheal diseases are a leading cause of morbidity and mortality in Africa. Although research documents the magnitude and pattern of diarrheal diseases are associated with weather in particular locations, there is limited quantification of this association in sub-Saharan Africa and no studies conducted in Mozambique. Our study aimed to determine whether variation in diarrheal disease was associated with precipitation in Mozambique. In secondary analyses we investigated the associations between temperature and diarrheal disease. We obtained weekly time series data for weather and diarrheal disease aggregated at the administrative district level for 1997–2014. Weather data include modeled estimates of precipitation and temperature. Diarrheal disease counts are confirmed clinical episodes reported to the Mozambique Ministry of Health (n = 7,315,738). We estimated the association between disease counts and precipitation, defined as the number of wet days (precipitation > 1 mm) per week, for the entire country and for Mozambique’s four regions. We conducted time series regression analyses using an unconstrained distributed lag Poisson model adjusted for time, maximum temperature, and district. Temperature was similarly estimated with adjusted covariates. Using a four-week lag, chosen a priori, precipitation was associated with diarrheal disease. One additional wet day per week was associated with a 1.86% (95% CI: 1.05–2.67%), 1.37% (95% CI: 0.70–2.04%), 2.09% (95% CI: 1.01–3.18%), and 0.63% (95% CI: 0.11–1.14%) increase in diarrheal disease in Mozambique’s northern, central, southern, and coastal regions, respectively. Our study indicates a strong association between diarrheal disease and precipitation. Diarrheal disease prevention efforts should target areas forecast to experience increased rainfall. The burden of diarrheal disease may increase with increased precipitation associated with climate change, unless additional health system interventions are undertaken.