Brain disorders-encompassing neurological, mental, and substance use disorders-account for 10 of the top 25 causes of disability worldwide in 2021. Despite such an impact, they have not been centrally analyzed in prior Global Burden of Disease (GBD) studies. This review synthesizes the latest disability-focused GBD study to quantify the prevalence and disability burden of 35 conditions from 2010 to 2021, a period marking the first decline in global health outcomes in three decades. It further incorporates disability metrics from 2021 to 2023 to contextualize post-pandemic trends. The review covers the prevalence and disability burden of neurological, mental, and substance use disorders along with COVID-19 using DALYs and YLDs metrics. From 2010 to 2021, Parkinson's, Alzheimer's, and motor neuron diseases (in neurological disorders), major depressive, anxiety, and eating disorders (in mental disorders), and opioid and drug use disorders (in substance use disorders) showed the greatest increases in age-adjusted prevalence rates across all sexes. In 2021, neurological disorders were the primary cause of DALYs, while depressive and anxiety disorders ranked as the 2 and 6 leading causes of global YLDs. Alzheimer's disease/dementias, Parkinson's disease, autism spectrum disorder, depressive and anxiety disorders, and opioid and drug use disorders show the largest increases in burden within their respective categories between 2010 and 2021. In the 2021-2023 extension analysis, disability data showed increases in prevalence and disability of several brain disorders, mostly anxiety disorders, while the COVID-19 disability burden declined markedly by 2023. Sex-specific burden metrics, key insights from each disorder, and limitations/confounds are discussed.