Earthquakes deep in the continental lithosphere are rare and hard to interpret in our current understanding of temperature control on brittle failure. The recent lithospheric mantle earthquake with a moment magnitude of 4.8 at a depth of ~75 km in the Wyoming Craton was exceptionally well recorded and thus enabled us to probe the cause of these unusual earthquakes. On the basis of complete earthquake energy balance estimates using broadband waveforms and temperature estimates using surface heat flow and shear wave velocities, we argue that this earthquake occurred in response to ductile deformation at temperatures above 750°C. The high stress drop, low rupture velocity, and low radiation efficiency are all consistent with a dissipative mechanism. Our results imply that earthquake nucleation in the lithospheric mantle is not exclusively limited to the brittle regime; weakening mechanisms in the ductile regime can allow earthquakes to initiate and propagate. This finding has significant implications for understanding deep earthquake rupture mechanics and rheology of the continental lithosphere.