At the beginning of December 2019, a new type of coronavirus emerged, SARS-CoV-2. This virus causes COVID-19, a highly contagious disease that can initially present asymptomatically and can also lead to death. Our ecological study goal was to evaluate the incidence, mortality, and lethality rates for COVID-19 between the states of Espírito Santo and Minas Gerais, with time series analysis using secondary and public databases on COVID-19 from January 2020 to December 2022. Prais–Winsten linear regression was used for trend analyses. In 2020, the rate in Espírito Santo was 2.19 times greater than in Minas Gerais. This trend continued in 2021, with Espírito Santo’s rate being 1.29 times greater. In 2022, Espírito Santo’s rate remained 2.65 times higher than Minas Gerais. Furthermore, Espírito Santo had the highest mortality, with the exception of 2021. In turn, Minas Gerais had the highest fatality rate throughout the analyzed pandemic period. The state of Espírito Santo had a higher incidence of COVID-19, as well as higher mortality when compared to the state of Minas Gerais. Furthermore, both states showed similar trends for mortality, lethality, and incidence in the years 2020 and 2021.