Among the groups most vulnerable to COVID-19 are Indigenous populations around the world, and in particular, the Mexican Indigenous population. We used public data made available by the General Directorate of Epidemiology of the Mexican Ministry of Health to compare the risk of COVID-19 mortality among the Indigenous and non-Indigenous Mexican population one and a half years into the pandemic. The analytical sample comprises 3,545,952 Mexicans who were diagnosed as infected with severe acute respiratory syndrome coronavirus-2 between March 18, 2020, and September 16, 2021, of which 1.0% (36,195) are Indigenous. Based on parametric survival models, our results show that the risk of death among Indigenous individuals is 52% higher than that of their non-Indigenous counterparts, regardless of age, sex, area of residence, health service, number of chronic diseases, and obesity status. These results suggest that certain structural conditions of the Mexican Indigenous population increase their vulnerability to the pandemic.