Control over the populations of singlet and triplet excitons is key to organic semiconductor technologies. In different contexts, triplets can represent an energy loss pathway that must be managed (i.e., solar cells, light-emitting diodes, and lasers) or provide avenues to improve energy conversion (i.e., photon upconversion and multiplication systems). A key consideration in the interplay of singlet and triplet exciton populations in these systems is the rate of intersystem crossing (ISC). In this work, we design, measure, and model a series of new electron acceptor molecules and analyze them using a combination of ultrafast transient absorption and ultrafast broadband photoluminescence spectroscopies. We demonstrate that intramolecular triplet formation occurs within several hundred picoseconds in solution and is accelerated considerably in the solid state. Importantly, ISC occurs with sufficient rapidity to compete with charge formation in modern organic solar cells, implicating triplets in intrinsic exciton loss channels in addition to charge recombination. Density functional theory calculations reveal that ISC occurs in triplet excited states characterized by local deviations from orbital π-symmetry associated with rotationally flexible thiophene rings. In disordered films, structural distortions, therefore, result in significant increases in spin−orbit coupling, enabling rapid ISC. We demonstrate the generality of this proposal in an oligothiophene model system where ISC is symmetry-forbidden and show that conformational disorder introduced by the formation of a solvent glass accelerates ISC, outweighing the lower temperature and increased viscosity. This proposal sheds light on the factors responsible for facile ISC and provides a simple framework for molecular control over spin states.