The mechanisms responsible for task failure during fatiguing submaximal contractions have not been clearly elucidated. Previous investigations have reported that muscle fatigue starts progressively from the beginning of the contraction due to linear reductions in motor unit discharge rate (Enoka & Duchateau, 2008). Nevertheless, other authors have reported non-linear variations in motor unit discharge rate (Mettler & Griffin, 2016), revealing the existence of two distinct phases of motor unit firing behaviour (Martinez-Valdes et al., 2020). By employing techniques of high-density surface electromyography (HDsEMG) motor unit decomposition, in combination with transcranial magnetic stimulation (TMS) we aimed to assess mechanisms responsible for this bi-phasic response in motor unit discharge rate during submaximal contractions. In addition, potential exercise-induced adjustments in discharge rate were also investigated. We performed three independent studies where we assessed motor unit responses to fatigue during 1) Isometric knee extension at 30% of the maximum voluntary contraction (MVC) until task failure, 2) Isometric dorsiflexion contraction at 25% of the MVC until task failure in combination with TMS and 3) Isometric knee extension until task failure (30% MVC) before and after 2 weeks of endurance training (cycling). In these studies, we observed that during fatigue 1) motor unit firing rate varied in a non-linear fashion, showing an initial reduction in discharge rate followed by a later increase in discharge rate. These variations in discharge rate were mirrored by opposite changes in motor unit twitch force (increase followed by decrease), 2) variations in discharge rate were related to non-linear variations in cortico-spinal excitability/inhibition 3) endurance training delayed the time in which these later increases in discharge rate occurred and this was associated with an increase in the time to task failure. These results show that during the development of fatigue there are diverse adjustments in motor unit firing properties, which are the result of the interplay between both motor unit contractile responses and changes in cortico-spinal excitability/inhibition. Interestingly, increases in task failure following endurance training seem to be related to a delayed increase in firing rate during fatiguing contractions.  Taken together, these findings show that the development of fatigue during submaximal contractions is not characterized by a progressive mechanism that occurs over the entire duration of the contraction but rather by a discrete time instant that marks the need to substantially increase the drive to the motor neuron pool, determining a reversal in motor unit firing behaviour.