The limits on maximal sustained energy expenditure in humans and other animals are unclear, but are of extreme interest in multiple fields because they constrain maximal reproductive output, thermoregulation, and physical activity. Here, we show that sustained expenditure in humans, measured as maximum sustained metabolic scope (SusMS), is a function of event duration. We compiled published measurements of total energy expenditure (TEE) and basal metabolic rate (BMR) from human endurance events, and extended the range of these observations with new data from adults running ~250km/week for 20 weeks in a transcontinental race. For events lasting 0.5 to 250+ days, SusMS decreases curvilinearly with event duration, plateauing below 3×BMR. This relationship differs from that of shorter events (e.g., marathons). Incorporating data from overfeeding studies, we find evidence for an alimentary energy supply limit in humans of ~2.5×BMR; greater expenditure requires drawing down the body’s energy stores. Transcontinental race data suggests humans can partially reduce TEE during long events to extend endurance.