Osteoarthritis (OA) is a major global health burden, affecting millions and causing significant disability. Understanding its trends and determinants is crucial for effective management and prevention. We analyzed data from the Global Burden of Diseases (GBD) study 2021 to assess OA incidence, Years Lived with Disability (YLDs), and age-standardized rates (ASIR/ASYR) from 1990 to 2021. We explored trends and determinants across gender, region, and Socio-Demographic Index (SDI) quintiles using Joinpoint regression, Age-Period-Cohort (APC) modeling, decomposition, and inequality analyses. The global incidence of OA surged from 20.9 million in 1990 to 46.6 million cases in 2021, with an AAPC of 0.29%. Correspondingly, YLDs escalated from 8.92 million to 21.30 million, reflecting an AAPC of 0.30%. Disparities exist across SDI quintiles, with higher rates observed in high SDI countries. Women consistently experience a higher burden compared to men. Asian regions demonstrate the fastest rise in ASYR. High BMI contributes significantly to OA burden, particularly in high SDI countries. The rising burden of OA necessitates urgent attention. Interventions targeting modifiable risk factors, such as obesity, and early detection and management strategies are crucial. Addressing gender disparities and health inequalities, particularly in high SDI countries, is essential for effective OA prevention and control.