The sensitivity of soil organic carbon (SOC) to changing environmental conditions represents a critical uncertainty in coupled carbon cycle–climate models. Much of this uncertainty arises from our limited understanding of the extent to which root–microbe interactions induce SOC losses (through accelerated decomposition or ‘priming’) or indirectly promote SOC gains (via ‘protection’ through interactions with mineral particles). We developed a new SOC model to examine priming and protection responses to rising atmospheric CO2. The model captured disparate SOC responses at two temperate free-air CO2enrichment (FACE) experiments. We show that stabilization of ‘new’ carbon in protected SOC pools may equal or exceed microbial priming of ‘old’ SOC in ecosystems with readily decomposable litter and high clay content (for example, Oak Ridge). In contrast, carbon losses induced through priming dominate the net SOC response in ecosystems with more resistant litters and lower clay content (for example, Duke). The SOC model was fully integrated into a global terrestrial carbon cycle model to run global simulations of elevated CO2effects. Although protected carbon provides an important constraint on priming effects, priming nonetheless reduced SOC storage in the majority of terrestrial areas, partially counterbalancing SOC gains from enhanced ecosystem productivity.