Unstable angina (UA) is one of the most dangerous types of coronary heart disease and has high mortality and morbidity rates worldwide. However, the diagnostic accuracy for UA is unsatisfactory in clinical practice. In this study, we investigated the application of plasma metabolomics in discovering potential biomarkers for the diagnosis of UA. Plasma samples from 45 UA and 43 atherosclerosis (AS) in-patients were collected and analyzed using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-QTOF/MS) in both positive and negative ion modes. Good separations were observed between the UA patients and AS controls. Tandem mass spectrometry experiments were carried out to identify biomarker candidates that contributed most to the discrimination (VIP > 1.2 and p < 0.05). Sixteen potential endogenous biomarkers for UA were identified, and those could perform a satisfactory diagnostic accuracy for discrimination between UA and AS patients (AUC = 0.9143). In the UA patients compared to the AS controls, the plasma concentrations of 12 metabolites were higher while the concentrations of four metabolites were lower. In conclusion, our study demonstrated that plasma metabolomics analyzed by RRLC-QTOF/MS had great potential in biomarker discovery for UA. These biomarkers could not only be helpful for the diagnosis of patients with UA, but also provide more information for further understanding of the metabolic processes of UA.