AbstractRayleigh optical activity (RayOA) spectroscopy promises to provide an elegant and robust analytical method to probe molecular stereochemistry. A careful selection of RayOA variants such as right‐angle depolarized ICP (incident circular polarization) or backscattering DCPI (in‐phase dual circular polarization) allows analysis of the anisotropic component of the scattered light. In this study, we show that calculated anisotropic Rayleigh optical activity quantities provide key advantages over isotropic chiroptical quantities (such as optical rotation and RayOA variants dominated by isotropic invariants): 1) higher sensitivity for probing the chiroptical tensor G′, 2) reduced dependence on small geometry changes, and 3) much less stringent computational demand for predicting an accurate sign than for optical rotation. Moreover, the stereochemical information provided by anisotropic RayOA and its invariants can be used to develop chirality descriptors because of the apparent correlation between structure/stereochemistry and the sign and magnitude of the anisotropic Rayleigh optical activity quantities.