Abstract: Extreme low-temperature events often have remarkable effects on human lives and crop growth. Therefore, it is important to analyze the causes of such events. This study utilized CN05.1 temperature observation data and ERA5 reanalysis data for the period 1980–2022 to examine the spatial and temporal distribution characteristics of the extreme low-temperature event that occurred in South China (20°N–30°N, 100°E–122°E) in May 2022. The circulation background and possible factors affecting this event were determined. The analysis revealed that the intensity of this event was strong, with the temperature being lower than three standard deviations compared with the average state of May 1980–2022. Besides, the cold lasted up to 31 days and affected an area of more than 1.5 million square kilometers. Thus, it was the strongest extreme low-temperature event since 1980. Further analysis revealed a significant wave train in the middle troposphere over the middle and high latitudes of Eurasia and an anomalous low pressure over South China, which caused the cold air in the middle and high latitudes to move deep south. Concurrently, because of the re-intensified La Niña in the equatorial Middle East Pacific, the convective suppression center became more westerly and stronger, and the related Rossby wave formed an anomalous anticyclone to the east of the Philippines. Subsequently, the southerly wind on the west side of this anticyclone transported warm and humid air from the ocean to South China. This air converged with the cold air to generate convection that significantly reduced the surface net shortwave radiation and further lowered the temperature. Thus, the extreme low-temperature event in South China in May 2022 was the result of the joint action of the circulation related to cold air activity and the Philippine anticyclone. The reproduced temperature obtained using the fitting equation constructed by considering these two factors reaches −2 times the standard deviation.