Historical and archeological data report that an earthquake was felt over the whole eastern Mediterranean on 21 July A.D. 365. The impact of the tsunami it generated, which may have caused several thousands of fatalities, has been widely studied, whereas the impact of the seismic waves has hardly been explored. Here, we present simulations of the ground motion caused by the A.D. 365 event at 316 sites now instrumented by seismological stations throughout Europe. The simulation approach is based on the modeling of a series of rupture scenarios coupled with empirical Green’s functions (EGFs) obtained at the stations from a recent 6.4 earthquake. The broadband and remarkably also the accelerometric records in urbanized areas can be exploited at distances as far as ∼2000 km. Then, we use three empirical models to estimate the macroseismic intensity across Europe from the simulated peak ground accelerations and peak ground velocities. The presence of stations in thick sedimentary basins (lower Danube valley, Po plain, urban accelerometric network in the alpine valley of Grenoble) shows that local basin amplification effects can dominate acceleration values at frequencies favorable to human earthquake perception (~0.5–1 Hz), even for basins located at more than 1500 km from the earthquake. Thus, our simulations indicate that the A.D. 365 earthquake was likely felt by the populations as far as the Po plain and as the city of Grenoble, about 1800 km away, and presumably in other large European basins such as the Pannonian basin. It is possible that the perception of the earthquake up to such distances contributed to its “universal” character perpetuated in archival sources. At closer distances (300–500 km), the simulated intensity levels indicate that the earthquake probably caused no damage.