Purpose: This study evaluated whether central motor drive during fatiguing exercise plays a role in determining performance and the development of neuromuscular fatigue during a subsequent endurance task. Methods: On separate days, 10 males completed three constant-load (80% peak power output), single-leg knee-extension trials to task failure in a randomized fashion. One trial was performed without preexisting quadriceps fatigue (CON), and two trials were performed with preexisting quadriceps fatigue induced either by voluntary (VOL; involving central motor drive) or electrically evoked (EVO; without central motor drive) quadriceps contractions (~20% maximal voluntary contraction (MVC)). Neuromuscular fatigue was assessed via pre-post changes in MVC, voluntary activation (VA), and quadriceps potentiated twitch force (Q tw,pot ). Cardiorespiratory responses and rating of perceived exertion were also collected throughout the sessions. The two prefatiguing protocols were matched for peripheral fatigue and stopped when Q tw,pot declined by ~35%. Results: Time to exhaustion was shorter in EVO (4.3 ± 1.3 min) and VOL (4.7 ± 1.5 min) compared with CON (10.8 ± 3.6 min,