Esophageal cancer remains a leading cause of cancer-related morbidity and mortality worldwide, with East and South Asia bearing a disproportionate burden. Despite global declines in age-standardized rates, these regions continue to face challenges due to sociodemographic and behavioral factors. Using Global Burden of Disease 2021 data, we analyzed trends in prevalence, incidence, mortality, and Disability-Adjusted Life Years (DALYs) from 1990 to 2021, emphasizing gender disparities and risk factor contributions. East Asia showed notable progress, with China reporting a 33.96% decrease in age-standardized incidence rate (ASIR) and a 45.78% decline in age-standardized mortality rate (ASMR). Korea also demonstrated improvements, whereas Taiwan recorded only a 4.69% reduction in ASIR but a striking 141.62% rise in ASMR. In South Asia, Bangladesh achieved a 32.74% fall in ASIR and Nepal a 19.01% decline, while Pakistan reported increases in both ASIR (+8.47%) and ASMR (+8.52%). Gender analyses revealed higher ASIR and ASMR among men, except in Pakistan where chewing tobacco drove higher female rates. Tobacco use accounted for 53.1% of the burden in South Asia and 55.2% in East Asia, dominated by smoking in East Asia and chewing tobacco in South Asia. These findings highlight the need for gender-sensitive interventions, stronger tobacco control, dietary improvement, and enhanced screening.