Background <p>Multiple myeloma (MM) is the second most common haematological malignancy worldwide. A comprehensive global analysis of MM based on diverse geographic locations and timeframes is lacking. This study aimed to provide the incidence, mortality rate, and disability-adjusted life years (DALYs) of MM, from 1990 to 2021, focusing on the age structure and temporal trends of the disease burden.</p> Methods <p>This study analysed the most recent MM data (1990 to 2021) from 204 countries and territories obtained from the Global Burden of Disease database. MM incidence, age-standardised mortality rate (ASMR), and DALYs were stratified by age, sex, and region to accurately reflect epidemiological trends and disease burden. The correlation between age-standardised rates and social population index was evaluated. To explore the influencing factors of MM, the annual percentage change (APC) and average APC rate (AAPC), as well as their corresponding 95% confidence intervals (UIs), were calculated.</p> Results <p>In 2021, there were approximately 35,000 cases of MM worldwide, with the highest numbers in China and Germany, with 47,003 and 32,010 cases, respectively. In 2021, Europe had the highest ASIR and ASPR, while North America had the highest ASMR and DALYs. Globally, age-standardized ASPR, ASMR, and DALYs all increased between 1990 and 2021. From 1990 to 2021, the number of cases, deaths, and disability-adjusted life-years due to MM were higher in males than in females. The higher the sociodemographic index, the higher the ASPR.</p> Conclusions <p>The global prevalence, ASIR, ASMR and DALYs of MM increased, showing significant regional disparities. These findings underscore the need for prevention in specific populations and emphasise the urgent need for new therapies to reduce ASIR and improve patient prognosis.</p>