Lignans in the drug Fructus Schisandrae chinensis (FSC) exhibit potent biological activities such as antihepatotoxic, antiasthmatic, and antigastric ulcer. An ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method has been developed to evaluate the quality of FSC through simultaneous qualitative and quantitative analysis of 15 lignans, including schizandrin A, B, and C; schizandrol A and B; gomisin B, C, D, E, G, H, J, and N; tigloylgomisin H; and angeloylgomisin H. The compounds were separated on a Zorbax Eclipse Plus C18 (2.1 × 100 mm, 1.8 μm) column with a gradient elution of acetonitrile and 0.1% formic acid. Lignans were identified through their retention times, accurate mass data, and characteristic ions by comparison with a reference substance. All calibration curves showed perfect linear regression (r2 > 0.99) within the test range. The limits of detection and quantitation fell in the ranges of 0.1–4 ng/mL for all the analytes with an injection of 10 μL. Good results were obtained with respect to repeatability (relative standard deviation <4.6%) and recovery (85.58–105.82%). Meanwhile, the entire sample analysis time was less than 10 min. This developed method provided a new basis for the overall assessment of the quality of FSC.