The solar minimum period between solar cycles 23 and 24 was the longest since the beginning of space-based measurements, and many manifestations of solar activity were unusually low. Thermospheric neutral density was about 30% lower than during the previous solar minimum, but changes in the ionosphere between the two solar minima are more controversial. Solar radiation, geomagnetic activity, and anthropogenic increases in greenhouse gases can all play a role in these changes. In this paper, we address the latter of these potential contributions the degree to which secular change driven by greenhouse gases, primarily CO2, could be responsible for the observed changes. New 3-D model simulations find a global mean density decrease at 400 km of 5.8% between the two recent solar minima, which is larger than earlier 1-D model results and in better agreement with observations. From these model simulations and from other observational work, we estimate that the contribution of secular change to global mean neutral density decrease between the two recent solar minima is less than ~6%. The contribution of secular change to the global average decrease of F region ionosphere peak density (NmF2) and altitude (hmF2), near midday, is estimated to be 1.5% and 1.5 km, respectively. However, secular changes in the ionosphere exhibit large variations with local time, geographic location, and season. The midday change of NmF2 seen in the model simulations ranged between +6% and −9% and the change of hmF2 ranged between +11 km and −11 km, depending on geographic location.