COVID-19 is considered by the World Health Organization to be a global public health emergency, which presents regional divergences that affect the epidemiological profile of the disease and are associated with political, economic, social and behavioral aspects. We aimed to analyze the epidemiological characteristics of the disease in the microregion of Uberlândia, Brazil, in order to determine risk factors that contributed to progression of SARS-CoV-2 virus. A cross-sectional study was conducted about micro- and macro-determinants combined with the significance analysis of suspected and confirmed cases in 18 municipalities during the epidemiological weeks (EW) 9 to 26. There were 34,046 notifications, of which 4935 (14.49%) people were diagnosed with COVID-19. Of these, 282 (5.71%) required hospital care and 40 (0.81%) died. Age and presence of associated comorbidities were decisive in the variations of incidence and lethality rates. In general, young people were the most affected and the elderly people, the most exposed to the serious and lethal form (p < 0.0001). Comorbidities such as diabetes and cardiopathies increased 33.5 times the death risk. The dispersion of the virus was centrifugal, in the inter as well as in the intra-municipal level. The disorderly implementation of municipal decrees applied in a decentralized manner in the municipalities seems to have contributed for the incidence rates increasing in the EW 25 and 26.