Background: Peru had the highest COVID-19 cumulative mortality rate worldwide. A greater disadvantage in the population infected with COVID-19 living under chronic hypoxia would be expected. However, previous studies reported a lower mortality at higher altitudes. Aim: The study assessed the relationship between altitude and COVID-19 mortality rate and case incidence in Peru at a district level from March 6, 2020, to February 28, 2022, and in its three waves. Subject and methods: This was an ecological, analytical study examining open data for 1874 Peruvian districts, ranging from 3 to 4675 m, with 3,372,962 COVID-19 cases and 212,017 deaths. Correlation statistics and a multivariate linear regression model were used to assess this relationship in this period and in three arbitrarily defined waves. Results: A negative coefficient of −0.00012 (95% CI −0.00015 to −0.00008) between altitude and mortality rate during the pandemic was obtained, corresponding to a 5.82% decrease in mortality for every 500 m. Similar findings for the three waves were observed, the first one with −0.000142 (95% CI −0.000178 to −0.000106); the second one, −0.000071 (95% CI −0.000101 to −0.000041); and the third one, −0.000017 (95% CI −0.000027 to −0.000006), equivalent to a decrease in mortality of 6.85%, 3.5%, and 0.85% for every 500 m. A coefficient of −0.0000905 (95% CI −0.000134 to −0.000047) between altitude and case incidence was observed, meaning a 4.42% decrease for every 500 m. In the first and third waves, a 5.06% and 3.92% decrease in incidence was found for every 500 m. Conclusion: Altitude had a protective effect against COVID-19 mortality and case incidence in Peru.