Ultra-endurance running provides numerous physiological, psychological, and nutritional challenges to the athlete and supporting practitioners. We describe the changes in physiological status, psychological condition, and nutritional intake over the course of two 100-mile running races, with differing outcomes: non-completion and completion. Athlete perception of pain, freshness, and motivation differed between events, independent of rating of perceived exertion. Our data suggest that the integration of multiple sensations (freshness, motivation, hunger, pain, and thirst) produce performance. Increases in carbohydrate feeding (+5 g·h −1) and protein intake (+0.3 g·kg −1) also likely contributed to successful completion of a 100-mile race, by reducing the fractional utilization of maximal oxygen uptake and satiating hunger, respectively. Nutritional data support the notion that the gut is a trainable, and critical organ with respect to ultra-endurance performance. Finally, we propose future research to investigate the rate at which peak feeding occurs throughout ultra-endurance events, as this may further serve to personalize sports nutrition strategies.