Background: A new method has been developed for the simultaneous determination of ferulic acid, senkyunolide A, and Z-ligustilide in Angelicae Sinensis Radix before and after sulfur-fumigation using quantitative analysis of multi-components by a single marker (QAMS). Materials and Methods: The feasibility and accuracy of QAMS were checked by the external standard method, and various high-performance liquid chromatographic instruments and chromatographic conditions were investigated to verify its applicability. Using ferulic acid as the internal reference substance, and the contents of senkyunolide A and Z-ligustilide were calculated according to relative correction factors by high-performance liquid chromatography. Meanwhile, the influence of sulfur-fumigation on these chemical components in Angelicae Sinensis Radix were evaluated and discriminated by chromatographic fingerprint and chemometrics. Results: There was no significant difference observed between the QAMS method and the external standard method. Furthermore, sulfur-fumigation reduced the contents of ferulic acid, senkyunolide A, and Z-ligustilide in Angelicae Sinensis Radix by some degree, and the sun-drying and sulfur-fumigation processing could be easily discriminated by chromatographic fingerprint and chemometrics. Conclusion: QAMS is a convenient and accurate approach to analyzing multi-component when reference substances are unavailable, simultaneously, chemometrics is an effective way to discriminate sun-dried and sulfur-fumigated Angelicae Sinensis Radix.