COVID-19 is a multifaceted disease whose local impacts align with the global context. In our study, we conducted a comprehensive analysis of the impact of COVID-19 in Lavras, a medium-sized municipality, a regional reference in health, located in the south of Minas Gerais state, Brazil. The data analyzed covered the period from 2020 to 2023, highlighting factors associated with transmission patterns and lethality in comparative terms with the global scenario. Data collection was carried out from official municipal publications, with an emphasis on information regarding the number of confirmed cases, deaths, and lethality rates. Genomic surveillance was conducted based on positive cases during the analysis period, and the results were published on GISAID. In 2020, there was an exponential increase in SARS-CoV-2 cases and associated deaths, with a lethality rate of 3.88%. The year 2021 witnessed a significant escalation, with a total of 8,762 cases and 135 deaths, presenting a lethality rate of 1.55%. The rapid spread of the disease led to high hospital occupancy for almost 90 days. In December 2021, the Omicron variant was identified, preceding a substantial increase in cases in early 2022, triggering a third wave resulting in 21,385 cases and 43 deaths. The lethality rate by the end of 2022 was 0.21%. The results highlight the capacity to confront COVID-19 and the virus's resilience, with a progressive reduction in lethality contrasting with the rise in SARS-CoV-2 infection incidence. This study provides a comprehensive view of COVID-19 patterns in Lavras over three years, emphasizing the importance of epidemiological surveillance and effective public health strategies to reduce the impact on the number of deaths from the disease, providing opportunities to address the disease.