The limits on maximum sustained energy expenditure are unclear but are of interest because they constrain reproduction, 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 measurements of total energy expenditure (TEE) and basal metabolic rate (BMR) from human endurance events and added new data from adults running ~250 km/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 suggest that humans can partially reduce TEE during long events to extend endurance.