The soil sink of molecular hydrogen is the largest and most uncertain term in the global atmospheric H2 budget. Lack of information about the mechanisms regulating this sink limits our ability to predict how atmospheric H2 may respond to future changes in climate or anthropogenic emissions. Here we present the results from a series of laboratory experiments designed to systematically evaluate and describe the temperature and soil moisture dependence of H2 uptake by soils from boreal forest and desert ecosystems. We observed substantial H2 uptake between −4°C and 0°C, a broad temperature optimum between 20°C and 30°C, a soil moisture optimum at approximately 20% saturation, and inhibition of uptake at both low and high soil moisture. A sigmoidal function described the temperature response of H2 uptake by soils between −15°C and 40°C. Based on our results, we present a framework for a model of the soil H2 sink.