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Ecosystem carbon losses from soil microbial respiration are a key component of global carbon cycling, resulting in the transfer of 40–70 Pg carbon from soil to the atmosphere each year. Because these microbial processes can feed back to climate change, understanding respiration responses to environmental factors is necessary for improved projections. We focus on respiration responses to soil moisture, which remain unresolved in ecosystem models. A common assumption of large-scale models is that soil microorganisms respond to moisture in the same way, regardless of location or climate. Here, we show that soil respiration is constrained by historical climate. We find that historical rainfall controls both the moisture dependence and sensitivity of respiration. Moisture sensitivity, defined as the slope of respiration vs. moisture, increased fourfold across a 480-mm rainfall gradient, resulting in twofold greater …