We estimate ground‐motion variability in the central and eastern United States (CEUS) by a deterministic physics‐based method, which has been previously used to simulate ground motions for the 5.8 Mineral, Virginia, and the 7.6 Bhuj, India (a tectonic analog for CEUS), earthquakes. Using the Next Generation Attenuation for Eastern United States (NGA‐East) ground‐motion database, we model additional motions for the CEUS and then simulate scenario 6.0, 6.5, 7.0, 7.5, and 8.0 events. To estimate the uncertainty using the physics‐based method, we use several realizations for the model parameters of mechanism, slip, stress drop, rupture velocity, source depth, and 1D velocity structure. Our median amplitudes for peak ground acceleration (PGA) and pseudospectral acceleration (PSA) at a variety of periods compare well with previous results from NGA‐East and the 2014 National Seismic Hazard Model (NSHM) ground‐motion prediction equation (GMPE) for the CEUS. The synthetic median is relatively centered within the range of the 13 GMPEs of the NGA‐East U.S. Geological Survey (USGS) GMPE. The standard deviation of ground motion (sigma) computed directly from all realizations ranges from to 0.85 natural log units. For most magnitudes, periods, and distances, our sigma falls in the range of values from the seed GMPEs of the 2014 NSHM GMPE but can be higher than, comparable to, or less than the ergodic sigma adopted by the NGA‐East USGS GMPE depending on the magnitude and period. Generally, we observe larger within‐event standard deviation than between‐events standard deviation , which agrees with other similar studies. There is no clear trend of either total sigma with magnitude or with distance, which is consistent with that found for central and eastern North America (CENA). The difference among sigmas for different magnitudes becomes larger with increasing period, and so does the difference between and .