Over four months in the winter of 2016-2017, 343 poultry farms in South Korea reported highly pathogenic avian influenza (HPAI) H5N6 occurrences, leading to the culling of 40 million poultry. Our study aimed to describe the spatial epidemiology of the 2016-2017 HPAI H5N6 outbreak in Gyeonggi Province, the most affected area in South Korea, comprising 35.9% (123) of the HPAI-infected poultry farms, to identify spatial risk factors for the increased probability of HPAI H5N6 occurrence, and to delineate areas with the highest likelihood of infection among different target poultry species. Although the poultry density was risk factor for the all species, rice paddy was only identified as risk factor for chicken and duck farms, not other species farms suggesting different biosecurity measures are required depending on the species. Although spatial effects of HPAI occurrence tended to be clustered within 16 km, the cluster range was reduced to 7 km when considering the identified risk factors, indicating a more geographically focused outbreak response when taking risk factors into account. The areas identified with the highest likelihood of infection can provide evidence, with accessibility to policymakers, to improve risk-based surveillance for HPAI. Our findings provide epidemiological understanding helpful in improving surveillance activity and assisting in the design of more cost-effective intervention policies related to future HPAI outbreaks in South Korea.