Terrestrial plant and soil respiration, or ecosystem respiration (Reco), represents a major CO2 flux in the global carbon cycle. However, there is disagreement in how Reco will respond to future global changes, such as elevated atmosphere CO2 and warming. To address this, we synthesized six years (2007–2012) of Reco data from the Prairie Heating And CO2 Enrichment (PHACE) experiment. We applied a semi-mechanistic temperature–response model to simultaneously evaluate the response of Reco to three treatment factors (elevated CO2, warming, and soil water manipulation) and their interactions with antecedent soil conditions [e.g., past soil water content (SWC) and temperature (SoilT)] and aboveground factors (e.g., vapor pressure deficit, photosynthetically active radiation, vegetation greenness). The model fits the observed Reco well (R2 = 0.77). We applied the model to estimate annual (March–October) Reco, which was stimulated under elevated CO2 in most years, likely due to the indirect effect of elevated CO2 on SWC. When aggregated from 2007 to 2012, total six-year Reco was stimulated by elevated CO2 singly (24%) or in combination with warming (28%). Warming had little effect on annual Reco under ambient CO2, but stimulated it under elevated CO2 (32% across all years) when precipitation was high (e.g., 44% in 2009, a ‘wet’ year). Treatment-level differences in Reco can be partly attributed to the effects of antecedent SoilT and vegetation greenness on the apparent temperature sensitivity of Reco and to the effects of antecedent and current SWC and vegetation activity (greenness modulated by VPD) on Reco base rates. Thus, this study indicates that the incorporation of both antecedent environmental conditions and aboveground vegetation activity are critical to predicting Reco at multiple timescales (subdaily to annual) and under a future climate of elevated CO2 and warming.