Human brucellosis continues to be a great threat to human health in China. The present study aimed to investigate the spatiotemporal distribution of human brucellosis in China from 2004 to 2019, to analyze the socioeconomic factors, meteorological factors and seasonal effect affecting human brucellosis incidence in different geographical regions with the help of spatial panel model, and to provide a scientific basis for local health authorities to improve the prevention of human brucellosis. The monthly reported number and incidence of human brucellosis in China from January 2004 to December 2019 were obtained from the Data Center for China Public Health Science. Monthly average air temperature and monthly average relative humidity of 31 provincial-level administrative units (22 provinces, 5 autonomous regions and 4 municipalities directly under the central government) in China from October 2003 to December 2019 were obtained from the National Meteorological Science Data Centre. The inventory of cattle, the inventory of sheep, beef yield, mutton yield, wool yield, milk yield and gross pastoral product of 31 provincial-level administrative units in China from 2004 to 2019 were obtained from the National Bureau of Statistics of China. The temporal and geographical distribution of human brucellosis was displayed with Microsoft Excel and ArcMap software. The spatial autocorrelation and hotspot analysis was used to describe the association among different areas. Spatial panel model was constructed to explore the combined effects on the incidence of human brucellosis in China. A total of 569,016 cases of human brucellosis were reported in the 31 provincial-level administrative units in China from January 2004 to December 2019. Human brucellosis cases were concentrated between March and July, with a peak in May, showing a clear seasonal increase. The incidence of human brucellosis in China from 2004 to 2019 showed significant spatial correlations, and hotspot analysis indicated that the high incidence of human brucellosis was mainly in the northern China, particularly in Inner Mongolia, Shanxi, and Heilongjiang. The results from spatial panel model suggested that the inventory of cattle, the inventory of sheep, beef yield, mutton yield, wool yield, milk yield, gross pastoral product, average air temperature (the same month, 2-month lagged and 3-month lagged), average relative humidity (the same month) and season variability were significantly associated with human brucellosis incidence in China. The epidemic area of human brucellosis in China has been expanding and the spatial clustering has been observed. Inner Mongolia and adjacent provinces or autonomous regions are the high-risk areas of human brucellosis. The inventory of cattle and sheep, beef yield, mutton yield, wool yield, milk yield, gross pastoral product, average air temperature, average relative humidity and season variability played a significant role in the progression of human brucellosis. The present study strengthens the understanding of the relationship between socioeconomic, meteorological factors and the spatial heterogeneity of human brucellosis in China, through which 'One Health'-based strategies and countermeasures can be provided for the government to tackle the brucellosis menace.