Summary: Worldwide, musculoskeletal (MSK) disorders are the second cause of living with disability. According to our data, in Mexico, MSK conditions are an important cause of disability, at national and state level. Preventive actions promoted by health systems to reduce the burden of MSK disorders are essential. Introduction: We describe premature mortality and disability due to musculoskeletal (MSK) disorders in Mexico at national and state level from 1990 to 2016. Methods: Using data from the global burden of disease study 2016 (GBD 2016), we present rates and trends in years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) caused by MSK disorders in Mexico by state from 1990 to 2016. The burden of MSK disorders was computed using standard GBD methodology. To compare the burden of MSK disorders across the country, states were grouped by sociodemographic index (SDI). Results: In Mexico, MSK disorders were the 3rd and 17th greatest cause of YLDs and YLLs in 2016, respectively, accounting for 1.95 million (95% UI 1.4–2.5) DALYs. Among all MSK disorders, low back and neck pain had the highest all-ages DALYs rate and represented 3.6% of total DALYs. All-ages YLLs and YLDs rates of MSK disorders were 234 and 37% higher in females (YLLs 102.2, 95% UI 79.9–110.7; YLDs 1677.9, 95% UI 1213.5–2209.4) than in males (YLLs 30.6, 95% UI 28.3–34.0; YLDs 1224.7, 95% UI 887.2–1608.3), respectively. Northern and high SDI states had higher rates of MSK disorders in comparison with southern and low SDI states. Only 16% of YLDs caused by all MSK disorders could be attributed to risk factors currently assessed in GBD. Conclusion: MSK conditions are an important cause of premature mortality and disability. Researcher engagement and cross-sectorial actions to address the burden of MSK disorders are essential.