The present study compared the fatigue-induced change of matched-amplitude thoracic evoked potential (TMEP) and lumbar evoked potential (LEP) following electrical stimulation. Ten participants performed a 3 × 3 min isometric knee extension contraction separated by 4 min of recovery at the level of EMG required to produce 50% maximal voluntary contraction (MVC) force at baseline. The TMEP and LEP were evoked during the ongoing contraction at baseline and every minute into the fatiguing protocol and during recovery. Both responses were also assessed during a transcranial magnetic stimulation (TMS) evoked silent period to elicit a TMS-TMEP and TMS-LEP to assess responses without the confounding influence of descending drive. The results displayed disparate kinetics of the TMS-TMEP and TMS-LEP throughout the fatiguing protocol. The TMS-TMEP was reduced at all time points during exercise ( P < 0.001), whereas the TMS-LEP was reduced at 2 min into set 1 and 1 min into sets 2 and 3 ( P ≤ 0.04). TMS-LEPs were higher than the TMS-TMEPs at most time points ( P ≤ 0.04). No change was observed in the TMEP or LEP. When evoked during the silent period, the reduction in TMEP is greater than the LEP during fatiguing isometric exercise. The disparate kinetics of change suggest that differential mechanisms are responsible for evoked responses to thoracic and lumbar stimulation. More research is required to identify the mechanisms responsible for the TMEP and LEP before precise inferences can be made on what fatigue-induced changes in these variables reflect. NEW & NOTEWORTHY Assessing spinal excitability using lumbar stimulation when measuring responses in lower limbs has been suggested as an alternative method that could circumvent the issues associated with thoracic stimulation. The present study compared responses to the two types of stimuli throughout a fatiguing protocol and demonstrated that lumbar evoked responses differ substantially from thoracic responses when measured in the absence of voluntary drive. These findings suggest that different mechanisms are responsible for evoked responses to thoracic and lumbar stimuli.