Soil moisture and temperature impose equally significant influences on soil heterotrophic respiration (HR). However, current modeling approaches often derive the functional relationships between soil HR and soil moisture content from incubation experiments and then apply them to spatial-temporal extrapolation without considering uncertainty associated with this approach. In this study, we devised a theory based on how soil moisture modulates diffusive delivery of soluble carbon and oxygen to microbes and show that it is possible to predict how soil moisture change will affect soil HR. Our predictions suggest that soil physical properties, e.g., soil texture and mineral surface abundances, affect soil HR. In particular, high soil clay content will cause soil HR to peak at higher soil moisture content, whereas more mineral surface area will cause soil HR to peak at lower soil moisture content and the transition from aerobic to anaerobic soil HR to be smoother. Most importantly, our predictions suggest that there is no simple multiplicative soil moisture effect on HR, as is commonly assumed. Rather, moisture control of soil HR is an emergent response resulting from interactions between microbes, substrates, soil physical and chemical properties, and even atmospheric conditions. We evaluate biases associated with commonly applied approaches, and conclude that models would benefit from using our new approach to represent soil HR dependencies on soil moisture.