Infectious diarrhea cases have increased during the past years in the Anhui Province of China, but little is known about its spatial cluster pattern and associated socioeconomic factors. We obtained county-level total cases of infectious diarrhea in 105 counties of Anhui in 2016 and computed age-adjusted rates. Socioeconomic factors were collected from the Statistical Yearbook. Hot spot analysis was used to identify hot and cold spot counties for infectious diarrhea incidence. We then applied binary logistic regression models to determine the association between socioeconomic factors and hot spot or cold spot clustering risk. Hot spot analysis indicated there were both significant hot spot (29 counties) and cold spot (18 counties) clustering areas for infectious diarrhea in Anhui (P < 0.10). Multivariate binary logistic regression results showed that infectious diarrhea hot spots were positively associated with per capita gross domestic product (GDP), with an adjusted odds ratio (AOR): 3.51, 95% CI: 2.09-5.91, whereas cold spots clustering were positively associated with the number of medical staffs (AOR: 1.18, 95% CI: 1.08-1.29) and negatively associated with the number of public health physicians (AOR: 0.27, 95% CI: 0.09-0.86). We identified locations for hot and cold spot clusters of infectious diarrhea incidence in Anhui, and the clustering risks were significantly associated with health workforce resources and the regional economic development. Targeted interventions should be carried out with considerations of regional socioeconomic conditions.