Danggui-Jianzhong decoction (DGJZ) is a famous classical traditional Chinese medicine formula, which ingredients are complex and the quality is difficult to control. Our study aimed to identify the overall chemical profile of DGJZ qualitatively by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and UPLC. A total of 77 components, including terpenoids, flavonoids, phenolic acids, gingerols and other components, were firstly detected and characterized by UPLC-Q-TOF-MS and 18 peaks marked after analyzing the UPLC fingerprint. Finally, paeoniflorin, liquiritin, ferulic acid, cinnamic acid, glycyrrhizic acid and 6-gingerol were quantified, which was validated in terms of linearity, precision, accuracy, repeatability and recovery. Taken together, the chemical constitutes of DGJZ were systematically identified and a reliable quantitative method coupled with fingerprint analysis was successfully employed for evaluating the holistic quality, which will provide a robust foundation for the quality control of DGJZ.