COVID-19 has affected all countries. Its containment represents a unique challenge for India due to a large population (> 1.38 billion) across a wide range of population densities. Assessment of the COVID-19 disease burden is required to put the disease impact into context and support future pandemic policy development. Here, we present the national-level burden of COVID-19 in India in 2020 that accounts for differences across urban and rural regions and across age groups. Input data were collected from official records or published literature. The proportion of excess COVID-19 deaths was estimated using the Institute for Health Metrics and Evaluation, Washington data. Disability-adjusted life years (DALY) due to COVID-19 were estimated in the Indian population in 2020, comprised of years of life lost (YLL) and years lived with disability (YLD). YLL was estimated by multiplying the number of deaths due to COVID-19 by the residual standard life expectancy at the age of death due to the disease. YLD was calculated as a product of the number of incident cases of COVID-19, disease duration and disability weight. Scenario analyses were conducted to account for excess deaths not recorded in the official data and for reported COVID-19 deaths. The direct impact of COVID-19 in 2020 in India was responsible for 14,100,422 (95% uncertainty interval [UI] 14,030,129–14,213,231) DALYs, consisting of 99.2% (95% UI 98.47–99.64%) YLLs and 0.80% (95% UI 0.36–1.53) YLDs. DALYs were higher in urban (56%; 95% UI 56–57%) than rural areas (44%; 95% UI 43.4–43.6) and in men (64%) than women (36%). In absolute terms, the highest DALYs occurred in the 51–60-year-old age group (28%) but the highest DALYs per 100,000 persons were estimated for the 71–80 years old age group (5481; 95% UI 5464–5500 years). There were 4,815,908 (95% UI 4,760,908–4,924,307) DALYs after considering reported COVID-19 deaths only. The DALY estimations have direct and immediate implications not only for public policy in India, but also internationally given that India represents one sixth of the world’s population.