The Tibetan medicine Wuwei Shaji powder (WWSJ) has been extensively applied to treating lung diseases such as chronic obstructive pulmonary disease (COPD). However, there are significant limitations in its quality control and evaluation. The purpose of this study was to analyze the overall chemical composition of WWSJ and to predict potential quality markers for WWSJ in the treatment of COPD. Using UHPLC-Q-Exactive Orbitrap-MS, 83 chemical constituents of WWSJ were identified or preliminarily characterized by 14 authentic reference standards, accurate mass counts, and characteristic fragment ions. In addition, serum pharmacology methods were employed to detect 13 blood-migrating components. Further network pharmacological research found that the potential mechanism of WWSJ in the treatment of COPD may be related to the regulation of the immune system and inflammatory response and identified 10 chemicals as key molecules in the treatment of COPD. Finally, the contents of six potential quality markers were determined simultaneously by high-performance liquid chromatography (HPLC). This study lays the foundation for further research on the mechanism of WWSJ in the treatment of COPD.