Background: Atractyloidis rhizome (cangzhu) was an important herb widely used in clinical application with different products, such as crude cangzhu (CZO), cangzhu pieces (CZP), bran frying cangzhu (BCZ), and Jiao cangzhu (JCZ). Objectives: To unscramble the phytochemical profiling of CZO, CZP, BCZ, and JCZ. Materials and Methods: In this paper, ultra-high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) technology and multivariate data analysis methods such as principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) were employed to screen the different components among CZO, CZP, BCZ, and JCZ. Results: As a result, CZO, CZP, BCZ, and JCZ were separated obviously in PCA plot, and a total of 101 components were identified successfully. Among them, 54 chemical markers, including isoleucine, citric acid, L-phenylalanine, atractyloside A, etc., discriminating among CZO, CZP, BCZ, and JCZ, were screened out. Conclusion: UHPLC-Q-TOF-MS/MS technology combined with PCA and OPLS-DA could be successfully applied in clarifying the different ingredients between crude drug and its processed products of traditional Chinese medicine (TCM). Importantly, the established method revealed the reasonability of processing theory in TCM.