We investigated the relationship between the systematic annual and semiannual variations in the ionosphere and thermosphere using a combination of data analysis and model simulation. A climatology of daytime peak density and height of the ionospheric F2 layer was obtained from GPS radio occultation measurements by the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) during 2007–2010. These measurements were compared to simulations by the NCAR Thermosphere-Ionosphere-Electrodynamics General Circulation Model (TIE-GCM). Model reproduction of the ionospheric annual and semiannual variations was significantly improved by imposing seasonal variation of eddy diffusion at the lower boundary, which also improves agreement with thermospheric density measurements. Since changes in turbulent mixing affect both the thermosphere and ionosphere by altering the proportion of atomic and molecular gases, these results support the proposition that composition change drives the annual/semiannual variation in both the neutral and ionized components of the coupled system.