Both first-generation αC-out and newer αC-in RAF inhibitors paradoxically activate BRAF kinase at subsaturating concentrations. Paradoxical activation by αC-in inhibitors is linked to the formation of BRAF dimers, but why activation rather than inhibition occurs remains unclear. We used biophysical methods tracking BRAF conformation and dimerization combined with thermodynamic modeling to define the allosteric coupling mechanism underlying paradoxical activation. Allosteric coupling between αC-in inhibitors and BRAF dimerization is both extremely strong and highly asymmetric, with the first inhibitor contributing the bulk of dimer promotion. This asymmetric allosteric coupling mechanism results in the induction of dimers in which only one protomer is inhibited while the other is activated. The type II class of RAF inhibitors currently in clinical trials are more asymmetrically coupled and possess greater activation potential than older type I inhibitors.19F NMR data demonstrate that the BRAF dimer displays dynamic conformational asymmetry, with only a subset of protomers locked in the αC-in state, explaining how the conformational effects of drug binding can efficiently drive BRAF dimerization and activation at substoichiometric concentrations.