Background Previous Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) studies have reported national health estimates for Ethiopia. Substantial regional variations in socioeconomic status, population, demography, and access to health care within Ethiopia require comparable estimates at the subnational level. The GBD 2019 Ethiopia subnational analysis aimed to measure the progress and disparities in health across nine regions and two chartered cities. Methods We gathered 1057 distinct data sources for Ethiopia and all regions and cities that included census, demographic surveillance, household surveys, disease registry, health service use, disease notifications, and other data for this analysis. Using all available data sources, we estimated the Socio-demographic Index (SDI), total fertility rate (TFR), life expectancy, years of life lost, years lived with disability, disability-adjusted life-years, and risk-factor-attributable health loss with 95% uncertainty intervals (UIs) for Ethiopia's nine regions and two chartered cities from 1990 to 2019. Spatiotemporal Gaussian process regression, cause of death ensemble model, Bayesian meta-regression tool, DisMod-MR 2.1, and other models were used to generate fertility, mortality, cause of death, and disability rates. The risk factor attribution estimations followed the general framework established for comparative risk assessment. Findings The SDI steadily improved in all regions and cities from 1990 to 2019, yet the disparity between the highest and lowest SDI increased by 54% during that period. The TFR declined from 6·91 (95% UI 6·59–7·20) in 1990 to 4·43 (4·01–4·92) in 2019, but the magnitude of decline also varied substantially among regions and cities. In 2019, TFR ranged from 6·41 (5·96–6·86) in Somali to 1·50 (1·26–1·80) in Addis Ababa. Life expectancy improved in Ethiopia by 21·93 years (21·79–22·07), from 46·91 years (45·71–48·11) in 1990 to 68·84 years (67·51–70·18) in 2019. Addis Ababa had the highest life expectancy at 70·86 years (68·91–72·65) in 2019; Afar and Benishangul-Gumuz had the lowest at 63·74 years (61·53–66·01) for Afar and 64.28 (61.99-66.63) for Benishangul-Gumuz. The overall increases in life expectancy were driven by declines in under-5 mortality and mortality from common infectious diseases, nutritional deficiency, and war and conflict. In 2019, the age-standardised all-cause death rate was the highest in Afar at 1353·38 per 100?000 population (1195·69–1526·19). The leading causes of premature mortality for all sexes in Ethiopia in 2019 were neonatal disorders, diarrhoeal diseases, lower respiratory infections, tuberculosis, stroke, HIV/AIDS, ischaemic heart disease, cirrhosis, congenital defects, and diabetes. With high SDIs and life expectancy for all sexes, Addis Ababa, Dire Dawa, and Harari had low rates of premature mortality from the five leading causes, whereas regions with low SDIs and life expectancy for all sexes (Afar and Somali) had high rates of premature mortality from the leading causes. In 2019, child and maternal malnutrition; unsafe water, sanitation, and handwashing; air pollution; high systolic blood pressure; alcohol use; and high fasting plasma glucose were the leading risk factors for health loss across regions and cities. Interpretation There were substantial improvements in health over the past three decades across regions and chartered cities in Ethiopia. However, the progress, measured in SDI, life expectancy, TFR, premature mortality, disability, and risk factors, was not uniform. Federal and regional health policy makers should match strategies, resources, and interventions to disease burden and risk factors across regions and cities to achieve national and regional plans, Sustainable Development Goals, and universal health coverage targets. Funding Bill & Melinda Gates Foundation.