A range of health-related and behavioral risk factors are associated with COVID-19 incidence and mortality. In the present study, we assess the association between incidence, mortality, and case fatality rate due to COVID-19 and the prevalence of hypertension, obesity, overweight, tobacco and alcohol use in the Peruvian population aged ≥15 years during the first and second year of the COVID-19 pandemic. In this ecological study, we used the prevalence rates of hypertension, overweight, obesity, tobacco, and alcohol use obtained from the Encuesta Demográfica y de Salud Familiar (ENDES) 2020 and 2021. We estimated the crude incidence and mortality rates (per 100,000 habitants) and case fatality rate (%) of COVID-19 in 25 Peruvian regions using data from the Peruvian Ministry of Health that were accurate as of 31 December 2021. Spearman correlation and lineal regression analysis was applied to assess the correlations between the study variables as well as multivariable regression analysis adjusted by confounding factors affecting the incidence and mortality rate and case fatality rate of COVID-19. In 2020, adjusted by confounding factors, the prevalence rate of obesity (β = 0.582; p = 0.037) was found to be associated with the COVID-19 mortality rate (per 100,000 habitants). There was also an association between obesity and the COVID-19 case fatality rate (β = 0.993; p = 0.014). In 2021, the prevalence of obesity was also found to be associated with the COVID-19 mortality rate (β = 0.713; p = 0.028); however, adjusted by confounding factors, including COVID-19 vaccination coverage rates, no association was found between the obesity prevalence and the COVID-19 mortality rate (β = 0.031; p = 0.895). In summary, Peruvian regions with higher obesity prevalence rates had higher COVID-19 mortality and case fatality rates during the first year of the COVID-19 pandemic. However, adjusted by the COVID-19 vaccination coverage, no association between the obesity prevalence rate and the COVID-19 mortality rate was found during the second year of the COVID-19 pandemic.