This study tested the hypothesis that during fatiguing quadriceps exercise, supraspinal fatigue develops late, is associated with both increased corticospinal excitability and inhibition and recovers quickly. Eight subjects performed 20 s contractions [15 s at 50% maximal voluntary contraction (MVC) followed by 5 s MVC] separated by a 10 s rest period until task failure. Transcranial magnetic stimulation (TMS) and electrical femoral nerve stimulation (PNS) were delivered ~2 s apart during 50% MVC, during MVC and after MVC in relaxed muscle. Voluntary activation was assessed by TMS (VATMS) immediately before and after exercise and then three times over a 6 min recovery period. During exercise, MVC and twitch force evoked by PNS in relaxed muscle decreased progressively to 48 ± 8 and 36 ± 16% of control values, respectively (both P < 0.01). Significant changes in voluntary activation assessed by PNS and twitch evoked by TMS during MVC were observed during the last quarter of exercise only (from 96.4 ± 1.7 to 86 ± 13%, P = 0.03 and from 0.76 ± 0.8 to 4.9 ± 4.7% MVC, P = 0.02, from baseline to task failure, respectively). The TMS-induced silent period increased linearly during both MVC (by ~79 ms) and 50% MVC (by ~63 ms; both P < 0.01). Motor-evoked potential amplitude did not change during the protocol at any force levels. Both silent period and VATMS recovered within 2 min postexercise, whereas MVC and twitch force evoked by PNS in relaxed muscle recovered to only 84 ± 9 and 73 ± 17% of control values 6 min after exercise, respectively. In conclusion, high-intensity single-joint quadriceps exercise induces supraspinal fatigue near task failure, with increased intracortical inhibition and, in contrast to previous upper-limb results, unchanged corticospinal excitability. These changes recover rapidly after task failure, emphasizing the need to measure corticospinal adaptations immediately at task failure to avoid underestimation of exercise-induced corticospinal changes.