An outbreak of the 2019 Novel Coronavirus Disease (COVID-19) in China caused by the emergence of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARSCoV2) spreads rapidly across the world and has negatively affected almost all countries including such the developing country as Vietnam. This study aimed to analyze the spatial clustering of the COVID-19 pandemic using spatial auto-correlation analysis. The spatial clustering including spatial clusters (high-high and low-low), spatial outliers (low-high and high-low), and hotspots of the COVID-19 pandemic were explored using the local Moran’s I and Getis-Ord’s G* i statistics. The local Moran’s I and Moran scatterplot were first employed to identify spatial clusters and spatial outliers of COVID-19. The Getis-Ord’s G* i statistic was then used to detect hotspots of COVID-19. The method has been illustrated using a dataset of 86,277 locally transmitted cases confirmed in two phases of the fourth COVID-19 wave in Vietnam. It was shown that significant low-high spatial outliers and hotspots of COVID-19 were first detected in the NorthEastern region in the first phase, whereas, high-high clusters and low-high outliers and hotspots were then detected in the Southern region of Vietnam. The present findings confirm the effectiveness of spatial auto-correlation in the fight against the COVID-19 pandemic, especially in the study of spatial clustering of COVID-19. The insights gained from this study may be of assistance to mitigate the health, economic, environmental, and social impacts of the COVID-19 pandemic.