Monitoring climatic changes in the thermosphere and ionosphere and understanding their causes is important for practical purposes. To support this effort and facilitate comparisons between observations and model results, a long transient simulation with the Whole Atmosphere Community Climate Model eXtension (WACCM-X) from 1950 to 2015 was conducted. This simulation used realistic variations in solar and geomagnetic activity, main magnetic field changes, and trace gas emissions, including CO 2 , thereby including all known drivers of upper atmosphere climate change. Analysis of the full 1950-2015 interval with a standard multilinear regression approach demonstrated difficulties in removing solar cycle effects sufficiently to obtain reliable trends. Results improved when an (F10.7a) 2 was included in the regression model, in addition to terms for F10.7a, K P , and the trend itself. Comparisons with previous studies and analysis of spatial variations in trend estimates confirmed that the increase in CO 2 concentration is the main driver of trends in thermosphere temperature and density, but at high (magnetic) latitudes effects of main magnetic field changes play a role as well, especially in the Northern Hemisphere. Spatial patterns of trends in h m F 2 , N m F 2 , and total electron content indicate a superposition of CO 2 and geomagnetic field effects, with the latter dominating trends in the region of ∼50-20 • N, ∼60 • W to 20 • E. Additional model experiments to investigate the indirect dynamical effects of climate change in the lower atmosphere (<50 km) on the upper atmosphere (>100 km) suggested that these effects are small and insignificant. However, current model limitations could mean that these effects are underestimated. Plain Language Summary A simulation with a state-of-the-art global model of the atmosphere from the surface up to about 500-km altitude was done for the period 1950-2015 to study climate change in the upper atmosphere (above 100-km altitude). The simulation included realistic variations in solar and geomagnetic activity, the Earth's magnetic field, and trace gas emissions, including CO 2. Solar and geomagnetic activity variations occur naturally as part of the ∼11-year solar cycle and have a large effect on the upper atmosphere. Still, by removing these effects as much as possible, we showed that the increase in CO 2 concentration is the main cause of cooling in the upper atmosphere, while effects of magnetic field changes also play a role near the poles, especially in the Northern Hemisphere. Long-term trends in the charged portion of the upper atmosphere, the ionosphere, are caused by both CO 2 and magnetic field effects, with the latter being most important in the region of ∼50 • S to 20 • N, ∼60 • W to 20 • E. Additional model experiments to investigate effects of climate change in the lower atmosphere (<50 km) on the upper atmosphere suggested that these are small. However, they might be underestimated by the model.