Birth defects remain the leading cause of stillbirth and infant mortality in China, especially in rural areas. The objective of this research is to seek evidence of clustering of cases of birth defects within a highly endemic area and to identify the environmental and landscape characteristics associated with increased risk for birth defects in Heshun county. This study uses four years of data, 1998-2001, to identify clusters of birth defects in Heshun county. A spatial scan statistic was employed to examine the spatial and spatio-temporal clustering of birth defects in the study area. Statistically significant clusters with high relative risk (RR = 2.981, p = 0.008) were identified using a spatial scan statistic. The spatial cluster located in southeast Heshun county has a radius of 7.52 km and includes 27 villages and 27 cases, accounting for 21.25% of the total cases during the study period. The methodology applied in this study was useful for evaluating the spatial distribution of birth defects in Heshun county from 1998-2001. The identified areas may be critical to control birth defects and may provide important direction for further study and targeted interventions.