Reverse intersystem crossing (RISC), the uphill spin-flip process from a triplet to a singlet excited state, plays a key role in a wide range of photochemical applications. Understanding and predicting the kinetics of such processes in vastly different molecular structures would facilitate the rational design of new materials. Here, we demonstrate a theoretical expression that successfully reproduces experimental RISC rate constants ranging over five orders of magnitude in twenty different molecules. We show that the spin flip occurs across the singlet–triplet crossing seam involving a higher-lying triplet excited state where the semi-classical Marcus parabola is no longer valid. The present model explains the counterintuitive substitution effects of bromine on the RISC rate constants of newly synthesized molecules, providing a predictive tool for material design.