We report the observation of a three-photon resonant transition of charge-carrier spins in an organic light-emitting diode using electrically detected magnetic resonance (EDMR) spectroscopy at room temperature. Under strong magnetic-resonant drive (drive field B1∼ static magnetic field B0), a B0-field swept EDMR line emerges when B0 is approximately three times the one-photon resonance center. Ratios of drive-induced shifts of this line to the shifts of two- and one-photon lines agree with analytical expressions derived from the Floquet Hamiltonian and confirm the nature of these three-photon transitions, enabling access of spin physics to a hitherto inaccessible domain of quantum mechanics.