Abstract Mental disorders are the leading cause of disease burden, affecting 13% of all people globally in 2019. However, there is scarce evidence on the burden of mental disorders in Nepal. This study used the Global Burden of Disease Study 2019 data to assess the prevalence and disability-adjusted life-years (DALYs) of mental disorders in Nepal between 1990 and 2019. In 2019, there were 3.9 million (95% UI: 3.6–4.3) people with mental disorders in Nepal. Major depressive disorders (1.1 million; 95% UI: 0.9–1.2 million) and anxiety disorders (0.9 million; 95% UI: 0.8–1.2 million) were the most prevalent mental disorders in 2019. Attention deficit hyperactive disorder, conduct disorder, and autism spectrum disorders were present twice as high in males than in females. The proportional contribution of mental disorders to the total disease burden has tripled between 1990 (1.79% of all DALYs) and 2019 (5.5% of all DALYs). In conclusion, the proportional contribution of mental disorders to total disease burden has increased significantly in the last three decades in Nepal, with apparent sex and age differentials in prevalence and DALY rates. Effective program and policy responses are required to prepare the health system for reducing the growing burden of mental health disorders in Nepal.