Objective To investigate the epidemiological characteristics of human brucellosis in Tacheng Prefecture, Xinjiang Uygur Autonomous Region, so as to provide insights into formulation of human brucellosis control measures. Methods The epidemiological data of human brucellosis cases in Tacheng Prefecture, Xinjiang Uygur Autonomous Region (excluding the Xinjiang Production and Construction Corps) from 2020 to 2023 were retrieved from the National Notifiable Infectious Diseases Reporting Information System, and population data in Tacheng Prefecture from 2020 to 2023 were collected from 2020 China Population Census by County. A hexagonal grid map was created at a township level using the R 4.5.0 software to examine the spatial distribution and spatial autocorrelation of human brucellosis cases, so as to identify statistically significant spatial clustering pat-terns and clusters. Results A total of 1 798 human brucellosis cases were reported in Tacheng Prefecture, Xinjiang Uygur Autonomous Region from 2020 to 2023, with an average annual incidence rate of 40.54/10⁵. Human brucellosis cases were predominantly detected during the period between March and August (1 291 cases, 71.80% of totally reported cases), and these cases were predominantly male (70.19%), individuals at ages of 30 to 60 years (73.14%), and farmers and herdsmen (86.32%). The highest annual average incidence of human brucellosis was found in Hoboksar Mongol Autonomous County (71.21/10⁵), and a high number of human brucellosis cases was reported in Shawan City and Wusu City (1 160 cases, 64.52% of total cases), which were epidemic-concentrated regions for human brucellosis. Spatial analysis of human brucellosis at a township scale revealed that human brucellosis cases exhibited spatial clustering patterns in Tacheng Prefecture each year from 2020 to 2023 (Moran's I = 0.27 to 0.44, all P values < 0.05). Hotspot townships were primarily concentrated in Shawan City and Wusu City and remained relatively stable, while cold-spot areas gradually expanded. Conclusions Human brucellosis remained highly prevalent in Tacheng Prefecture, Xinjiang Uygur Autonomous Region from 2020 to 2023. Targeted management of sources of infection and high-risk individuals is recommended for human brucellosis control.