AbstractRecent measurements of GPS‐derived total electron content (TEC) reveal acoustic wave periods of ∼1–4 min in the F region ionosphere following natural hazard events, such as earthquakes, severe weather, and volcanoes. Here we simulate the ionospheric responses to infrasonic‐acoustic waves, generated by vertical accelerations at the Earth's surface or within the lower atmosphere, using a compressible atmospheric dynamics model to perturb a multifluid ionospheric model. Response dependencies on wave source geometry and spectrum are investigated at middle, low, and equatorial latitudes. Results suggest constraints on wave amplitudes that are consistent with observations and that provide insight on the geographical variability of TEC signatures and their dependence on the geometry of wave velocity field perturbations relative to the ambient geomagnetic field. Asymmetries of responses poleward and equatorward from the wave sources indicate that electron perturbations are enhanced on the equatorward side while field aligned currents are driven principally on the poleward side, due to alignments of acoustic wave velocities parallel and perpendicular to field lines, respectively. Acoustic‐wave‐driven TEC perturbations are shown to have periods of ∼3–4 min, which are consistent with the fraction of the spectrum that remains following strong dissipation throughout the thermosphere. Furthermore, thermospheric acoustic waves couple with ion sound waves throughout the F region and topside ionosphere, driving plasma disturbances with similar periods and faster phase speeds. The associated magnetic perturbations of the simulated waves are calculated to be observable and may provide new observational insight in addition to that provided by GPS TEC measurements.