Drug use disorders (DUDs) have been a public health crisis which strongly impacted community health and socio-economic development. However, there are few studies based on the latest global data to show changes in the disease burden due to DUDs, specifically investigating associations between the country-level socio-economic factors and the burden of DUDs.Data of DUDs were extracted from the Global Burden of Disease Study 2019 database to explore the trends of the disease burden due to DUDs from 1990 to 2019. Univariate linear regression and stepwise multiple linear regression analysis were performed to analyze the correlations between burden due to DUDs and country-level socio-economic factors.Globally, the number of disability-adjusted life-years (DALYs) caused by DUDs approximately increased by 2.6% yearly from 1990 to 2019, though the age-standardized DALY rate has not changed significantly in the past 30 years. The age-standardized DALY rate of opioid use disorders showed an upward trend during the past 30 years and was highest among 5 types of DUDs in 2019. Inequality-adjusted human development index (β = 15.9, 95% confidence interval [CI]: 12.9-18.9, P < 0.001) was identified as the key risk factor associated with square-root transformed age-standardized DALY rate of DUDs.Global burden due to DUDs has increased significantly over the past 30 years. More effective targeted public health policies should be formulated to manage the public health challenge of DUDs, especially in developed countries and territories.