Aims: Pancreatic cancer (PC) is a malignant tumor with a strong invasive nature and low survival rate. We aimed to estimate the PC burden at the global, regional, and national levels in 204 countries from 1990 to 2019. Methods: Detailed data, including the incidence, death, and disability-adjusted life years (DALYs), were analyzed from the Global Burden of Diseases Study 2019. Results: Globally, there were 530,297 (486,175–573,635) incident cases and 531,107 (491,948–566,537) deaths from PC in 2019. The age-standardized incidence rate (ASIR) was 6.6 (6–7.1), and the age-standardized mortality rate (ASMR) was 6.6 (6.1–7.1) per 100,000 person-years. PC caused 11,549,016 (10,777,405–12,338,912) DALYs, with an age-standardized rate of 139.6 (130.2–149.1) per 100,000 person-years. There were increases in estimated annual percentage changes (EAPCs) of ASIR (0.83; 0.78–0.87), ASMR (0.77; 0.73–0.81), and age-standardized DALYs rate (ASDR) (0.67; 0.63–0.71). The global number of incident cases increased by 168.7%, from 197,348 (188,604–203,971) to 530,297 (486,175–573,635); the number of deaths increased by 168.2% from 198,051 (189,329–204,763) to 531,107 (491,948–566,537); and total DALYs increased by 148.5% from 4,647,207 (4,465,440–4,812,129) to 11,549,016 (10,777,405–12,338,912). East Asia and China recorded the highest number of incident cases, deaths, and DALYs. The proportion of deaths was attributable to smoking (21.4%), elevated fasting glucose (9.1%), and high BMI (6%). Conclusions: Our study updated the epidemiological trends and risk factors for PC. PC remains a major hazard to the sustainability of health systems worldwide, with an increasing incidence rate and mortality from 1990 to 2019. More targeted strategies are required to prevent and treat PC.