Background For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. Methods The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010–23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Findings Total numbers of global DALYs grew 6·1% (95% UI 4·0–8·1), from 2·64 billion (2·46–2·86) in 2010 to 2·80 billion (2·57–3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0–14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31–1·61) global DALYs in 2010, increasing to 1·80 billion (1·63–2·03) in 2023, alongside a concurrent 4·1% (1·9–6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176–209] DALYs), stroke (157 million [141–172]), and diabetes (90·2 million [75·2–107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0–107·5]), depressive disorders (26·3% [11·6–42·9]), and diabetes (14·9% [7·5–25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837–917) in 2010 to 681 million (642–736) in 2023, and a 25·8% (22·6–28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7–61·0) for diarrhoeal diseases, 42·9% (38·0–48·0) for HIV/AIDS, and 42·2% (23·6–56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6–22·0) and 24·8% (7·4–36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7–19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18–1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation—with high SBP accounting for 8·4% (6·9–10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories—behavioural, metabolic, and environmental and occupational—risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8–37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0–11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023—eg, declining by 54·4% (38·7–65·3) for unsafe sanitation, 50·5% (33·3–63·1) for unsafe water source, and 45·2% (25·6–72·0) for no access to handwashing facility, and by 44·9% (37·3–53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [–2·7 to 15·6]; non-significant). Interpretation Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors—eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG—including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic—the complex interaction of multiple health risks, social determinants, and systemic challenges—will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. Funding Gates Foundation and Bloomberg Philanthropies.