Outdoor air pollution, particularly volatile organic compounds (VOCs), significantly contributes to the global health burden. Previous analyses of VOC exposure have typically focused on regional and national scales, thereby limiting global health burden assessments. In this study, we utilized a global chemistry-climate model to simulate VOC distributions and estimate related cancer risks from 2000 to 2019. Our findings indicated a 10.2% rise in global VOC emissions during this period, with substantial increases in Sub-Saharan Africa, the Rest of Asia, and China, but decreases in the U.S. and Europe due to reductions in the transportation and residential sectors. Carcinogenic VOCs such as benzene, formaldehyde, and acetaldehyde contributed to a lifetime cancer burden affecting 0.60 [95% confidence interval (95CI): 0.40–0.81] to 0.85 [95CI: 0.56–1.14] million individuals globally. We projected that between 36.4% and 39.7% of the global population was exposed to harmful VOC levels, with the highest exposure rates found in China (82.8–84.3%) and considerably lower exposure in Europe (1.7–5.8%). Open agricultural burning in less-developed regions amplified VOC-induced cancer burdens. Significant disparities in cancer burdens between high-income and low-to-middle-income countries were identified throughout the study period, primarily due to unequal population growth and VOC emissions. These findings underscore health disparities among different income nations and emphasize the persistent need to address the environmental injustice related to air pollution exposure.