Background: Mesothelioma, as a lethal consequence of asbestos exposure, poses a significant threat to high-risk populations. The Global Burden of Disease (GBD) 2021 update provides an opportunity to examine current mesothelioma epidemiology and assess whether asbestos bans have effectively reduced mesothelioma incidence over a longer time span than covered in existing literature. Methods: Annual cases and age-standardized rates (ASRs, reported per 100,000 person-years) of incidence, death, disability-adjusted life-years, and probability of death associated with mesothelioma among different age groups were obtained from patients in 204 countries and territories diagnosed with mesothelioma between 1990 and 2021. Estimated annual percentage changes (EAPCs) and period analysis of ASRs were employed to evaluate temporal trends in incidence and mortality. Data on global asbestos consumption and bans were collected from various sources to investigate their relationship with mesothelioma burdens. Results: In 2021, global incident cases of mesothelioma slightly increased to 31,908 [29,643, 34,115], with 23,184 [21,553, 24,941] in males and 8,724 [7,784, 9,580] in females, up from 31,173 [28,821, 33,090] in 2019, and approximately double the number in 1990 (16,493 [15,325, 17,783]). Australasia, Western Europe, and Southern Sub-Saharan Africa ranked in the top three for all ASRs. The United Kingdom and Australia had the highest ASRs globally, while the Northern Mariana Islands, El Salvador, Syrian Arab Republic, Iran (Islamic Republic of), Saudi Arabia, and Palestine had the lowest ASRs in 2021. Most countries with asbestos bans continued to exhibit declining trends in ASRs from 2019 to 2021. Conclusions: Global asbestos bans have demonstrated sustained effectiveness in controlling mesothelioma. Accelerated implementation of asbestos bans in developing nations coupled with deeper exploration of meso-thelioma pathogenesis would aid in enhancing primary prevention efforts. Although the mesothelioma burden is more severe in high-income regions, ASRs have decreased more notably in high and upper-middle socio-de-mographic indexes (SDIs) tiers with generally more comprehensive and earlier asbestos bans compared to other locations. The burden of female mesothelioma has shown slower remission compared to males in many regions recently, underscoring the importance of non-occupational exposures.