BACKGROUND: Brucellosis is a common zoonotic disease in Iran. This study aimed to investigate the epidemiological characteristics of human brucellosis and its affecting factors in Khorasan Razavi province, an endemic region in north-eastern Iran. METHODS: In this descriptive-analytical study, the data of 15,334 brucellosis cases in Khorasan Razavi province from 2016 to 2022 were analyzed. Descriptive analysis and geographic information system (GIS)-based Inverse Distance Weighting (IDW) were conducted to assess the demographic factors and spatial modeling of the study population. Chi-squared and Fisher's exact tests were used for intergroup comparisons. A latent class cluster analysis (LCCA) in R programming language (poLCA) was employed to identify clusters and better understand the factors affecting the disease. RESULTS: The results indicated that most of the brucellosis cases had been registered from 2020 to 2022 (26.5 %, 21.4 %, and 14.5 % of the total cases). The average incidence rate of brucellosis during the study period was 33.57 cases per 100,000 population. Over 84 % of the cases in clusters 1 and 3 (60.4 % of the whole study population) were males who often lived in rural areas. Only 29.3 % of the patients had a job related to livestock. These findings are consistent with the data on the consumption of unpasteurized dairy products and the history of animal vaccination. CONCLUSION: Brucellosis cannot be significantly controlled by merely focusing on people working in the livestock industry, highlighting the impact of herd vaccination, and promoting public awareness, especially among housewives and younger people. Meanwhile, proper handling and disposal of infected animals, regular quarantine and inspection of livestock, and sanitization of animal environments have been recommended.