Traditional Chinese medicine formula granules (TCMFGs) are the advanced dosage forms of the single traditional Chinese herbal decoction pieces, which are widely used for clinical treatment in China. With the clinical application of TCMFG, Erchen decoction (ECD), a classic traditional Chinese medicine (TCM) formula treating phlegm–dampness syndrome, is treated as TCM formula granules instead of herb decoction pieces. However, the chemical profiles and chemical consistency between TCM formula granules ECD and herbal decoction pieces are still unclear. To clarify the chemical profiles in TCM formula granules ECD, the ultra‐high performance liquid chromatography‐Q‐Exactive Orbitrap tandem mass spectrometry technology was used to characterize the chemical profiles of TCM formula granules ECD, and nine characteristic chemical components were further determined. Our exciting finding indicated that a total of 64 components were quantified and glycyrrhizic acid, hesperidin, liquiritigenin, and nobiletin were found to be the major compounds in TCM formula granules ECD and might be the pharmacodynamic material basis of ECD for phlegm–dampness syndrome treatment. The study is to explore the chemical profile and the major compounds quantitatively analysis of TCM formula granules ECD for the first time, which provides a valuable knowledge for the quality control and clinical application on TCM formula granules ECD.