BACKGROUND: A warming climate throughout the 21st century makes ambient high temperature exposure a major threat to population health worldwide. Mitigating the health impact of high temperature requires a timely, comprehensive and reliable assessment of disease burden globally, regionally and temporally. AIM: Based on Global Burden of Disease (GBD) Study 2019, this study aimed to evaluate the disease burden attributable to high temperature from various epidemiology perspectives. METHODS: A three-stage analysis was undertaken to investigate the number and age-standardized rates of death and disability-adjusted life years (DALY) attributable to high temperature from GBD Study 2019. First, we reported the high temperature-related disease burden for the whole world and for different groups by gender, age, region, country and disease. Second, we examined the temporal trend of the disease burden attributable to high temperature from 1990 to 2019. Finally, we explored if and how the high temperature-related disease burden was modified by a number of country-level indicators. RESULTS: Globally, high temperature accounted for 0.54% of death and 0.46% of DALY in 2019, equating to the age-standardized rates of death and DALY (per 100,000 population) of 3.99 (95% uncertainty interval (UI): 2.88, 5.93) and 156.81 (95% UI: 107.98, 261.98), respectively. In 2019, the high temperature-related DALY and death rates were the highest for lower respiratory infections, although they showed a downward trend. In contrast, during 1990-2019, high temperature-related non-communicable diseases burden exhibited an upward trend. Meanwhile, the disease burden attributable to high temperature varied spatially, with the heaviest burden in regions with low sociodemographic index (SDI) and the lightest burden in regions with high SDI. In addition, high temperature-related disease burden appeared to be higher in a country with a higher population density and PM(2.5) concentration background but lower in a country with a higher density of greenness. CONCLUSION: This study for the first time provided a comprehensive understanding of the global disease burden attributable to high temperature, underscoring the policy priority to protect human health worldwide in the context of global warming with particular attention to vulnerable countries or regions as well as susceptible population and diseases.