We compute the next-to-next-to-leading order spin-orbit contributions in the total energy flux emitted in gravitational waves by compact binary systems. Such contributions correspond to the post-Newtonian order 3.5PN for maximally spinning compact objects. Continuing our recent work on the next-to-next-to-leading spin-orbit terms at the 3.5PN order in the equations of motion, we obtain the spin-orbit terms in the multipole moments of the compact binary system up to the same order within the multipolar post-Newtonian wave generation formalism. Our calculation of the multipole moments is valid for general orbits and in an arbitrary frame, the moments are then reduced to the center-of-mass frame and the resulting energy flux is specialized to quasi-circular orbits. The test-mass limit of our final result for the flux agrees with the already known Kerr black hole perturbation limit. Furthermore, the various multipole moments of the compact binary reduce in the one-body case to those of a single-boosted Kerr black hole. We briefly discuss the implications of our result for the gravitational wave flux in terms of the binary’s phase evolution, and address its importance for the future detection and parameter estimation of signals in gravitational wave detectors.