Introduction <p>In this work, we aim to evaluate the trends and cross-country inequalities of the global trachoma burden from 1990 to 2021 and to project its burden to 2040.</p> Methods <p>This study was a systematic analysis of the Global Burden of Diseases Study (GBD) 2021. Estimates for the prevalence and disability-adjusted life-years (DALYs) of trachoma were extracted from the GBD 2021 database. Epidemiological characteristics of trachoma were reported at the global, regional, and national levels. Trend analysis, decomposition analysis, and health inequality analysis were used. The global trachoma burden was further projected to 2040 via Bayesian age–period–cohort analysis.</p> Results <p>Globally, 1,414,047 people were estimated to have trachoma in 2021, with an age-standardized prevalence rate of 16.37 per 100,000 population. Between 1990 and 2021, the prevalent cases and DALY numbers of trachoma decreased by 30.2% and 34.4%, respectively. In 2021, Eastern Sub-Saharan Africa was the region, and Ethiopia was the country with the highest number of trachoma cases. Decomposition analysis revealed that the reduction in the global burden was attributed primarily to epidemiological changes. From 1990 to 2021, countries with lower sociodemographic indices (SDIs) disproportionately bore the heaviest burden. While the prevalence and DALY rates are projected to decrease from 2022 to 2040, the prevalent cases and DALY numbers are expected to increase.</p> Conclusions <p>Over the past three decades, the global burden of trachoma has decreased significantly, but SDI-related inequalities among countries have persisted. Despite reductions in the prevalence rate, the number of patients with trachoma is projected to increase from 2022 to 2040. Our study provides valuable insights into the elimination of trachoma worldwide.</p>