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Soil organic carbon harbors three times as much carbon as Earth’s atmosphere, and its decomposition is a potentially large climate change feedback and major source of uncertainty in climate projections. The response of whole-soil profiles to warming has not been tested in situ. In this deep warming experiment in mineral soil, CO2 production from all soil depths increased significantly with 4°C warming—annual soil respiration increased by 34-37%. All depths responded to warming with similar temperature sensitivities, driven by decomposition of decadal-aged carbon. Whole-soil warming reveals a larger soil respiration response than many in situ experiments, most of which only warm the surface soil, and models.