<p>The Tibetan Plateau, as an important global ecological security barrier, has experienced increasing ozone (O₃) concentrations in some regions in recent years, posing important impacts on regional ecosystem stability and human health. In this study, multi-source datasets and the BenMAP-CE model were combined to investigate land-use change characteristics and to evaluate the pollution characteristics, driving factors, and health effects of ozone and its precursors over the Tibetan Plateau. The results showed that the expansion of grassland was mainly converted from woodland. Except for ozone, which exhibited a positive weekend effect, both nitrogen dioxide (NO₂) and formaldehyde (HCHO) showed negative weekend effects. GDP, completed housing and car ownership were identified as the major anthropogenic factors influencing O₃–NO₂–HCHO, while NDVI, solar radiation, snow cover, and wind speed were highly correlated with pollutant variations. Ozone pollution in the study area caused annual average premature deaths of 3054, 401, 1114, and 2140 from all-cause, lung cancer, respiratory and cardiovascular diseases, respectively. In addition, exogenous transport in Zedang during the warm season was mainly influenced by northwestern and southern airflow pathways. This study reveals the spatiotemporal characteristics and potential driving mechanisms of ozone and its precursors over the Tibetan Plateau, providing scientific support for coordinated ozone pollution control and volatile organic compounds-nitrogen oxides (VOCs–NO_x) emission reduction strategies in plateau regions.</p>