•There is a heterogeneous spatial and temporal distribution pattern of dengue cases in China.•The primary clusters included 13 counties in Guangdong Province and the secondary clusters covered 14 counties in Yunnan Province.•High risk regions were located in Guangdong and Yunnan Provinces.•Meteorological and environmental factors had nonlinear relationships with dengue incidence. To identify the high risk spatiotemporal clusters of dengue cases and explore the associated risk factors. Monthly indigenous dengue cases in 2005-2017 were aggregated at county level. Spatiotemporal cluster analysis was used to explore dengue distribution features using SaTScan9.4.4 and Arcgis10.3.0. In addition, the influential factors and potential high risk areas of dengue outbreaks were analyzed using ecological niche models in Maxent 3.3.1 software. We found a heterogeneous spatial and temporal distribution pattern of dengue cases. The identified high risk region in the primary cluster covered 13 counties in Guangdong Province and in the secondary clusters included 14 counties in Yunnan Province. Additionally, there was a nonlinear association between meteorological and environmental factors and dengue outbreaks, with 8.5%–57.1%, 6.7%–38.3% and 3.2%–40.4% contribution from annual average minimum temperature, land cover and annual average precipitation, respectively. The high risk areas of dengue outbreaks mainly are located in Guangdong and Yunnan Provinces, which are significantly shaped by environmental and meteorological factors, such as temperature, precipitation and land cover.