Ionospheric day-to-day variability is a ubiquitous feature, even in the absence of appreciable geomagnetic activities. Although meteorological perturbations have been recognized as an important source of the variability, it is not well represented in previous modeling studies and the mechanism is not well understood. This study demonstrates that the thermosphere-ionosphere-mesosphere-electrodynamics general circulation model (TIME-GCM) constrained in the stratosphere and mesosphere by the hourly whole atmosphere community climate model (WACCM) simulations is capable of reproducing observed features of day-to-day variability in the thermosphere-ionosphere. Realistic weather patterns in the lower atmosphere in WACCM were specified by Modern Era Retrospective Reanalysis for Research and Application (MERRA). The day-to-day variations in mean zonal wind, migrating and nonmigrating tides in the thermosphere, vertical and zonal E × B drifts, and ionosphere F2 layer peak electron density (NmF2) are examined. The standard deviations of the drifts and NmF2 show local time and longitudinal dependence that compare favorably with observations. Their magnitudes are 50% or more of those from observations. The day-to-day thermosphere and ionosphere variability in the model is primarily caused by the perturbations originated in lower atmosphere, since the model simulation is under constant solar minimum and low geomagnetic conditions.