Clarification of the chemical composition of traditional Chinese medicine formulas (TCMFs) is a challenge due to the variety of structures and the complexity of plant matrices. Herein, an integrated strategy was developed by hyphenating ultra-performance liquid chromatography (UPLC), quadrupole time-of-flight (Q-TOF), hybrid triple quadrupole-linear ion trap mass spectrometry (Qtrap-MS), and the novel post-acquisition data processing software UNIFI to achieve automatic, rapid, accurate, and comprehensive qualitative and quantitative analysis of the chemical components in TCMFs. As a proof-of-concept, the chemical profiling of Baoyuan decoction (BYD), which is an ancient TCMF that is clinically used for the treatment of coronary heart disease that consists of Ginseng Radix et Rhizoma, Astragali Radix, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, and Cinnamomi Cortex, was performed. As many as 236 compounds were plausibly or unambiguously identified, and 175 compounds were quantified or relatively quantified by the scheduled multiple reaction monitoring (sMRM) method. The findings demonstrate that the strategy integrating the rapidity of UNIFI software, the efficiency of UPLC, the accuracy of Q-TOF-MS, and the sensitivity and quantitation ability of Qtrap-MS provides a method for the efficient and comprehensive chemome characterization and quality control of complex TCMFs.