This study investigates whether spinal manipulation leads to neural plastic changes involving cortical drive and the H-reflex pathway. Soleus evoked V-wave, H-reflex, and M-wave recruitment curves and maximum voluntary contraction (MVC) in surface electromyography (SEMG) signals of the plantar flexors were recorded from ten subjects before and after manipulation or control intervention. Dependent measures were compared with 2-way ANOVA and Tukey’s HSD as post hoc test, p was set at 0.05. Spinal manipulation resulted in increased MVC (measured with SEMG) by 59.5 ± 103.4 % (p = 0.03) and force by 16.05 ± 6.16 4 % (p = 0.0002), increased V/M max ratio by 44.97 ± 36.02 % (p = 0.006), and reduced H-reflex threshold (p = 0.018). Following the control intervention, there was a decrease in MVC (measured with SEMG) by 13.31 ± 7.27 % (p = 0.001) and force by 11.35 ± 9.99 % (p = 0.030), decreased V/M max ratio (23.45 ± 17.65 %; p = 0.03) and a decrease in the median frequency of the power spectrum (p = 0.04) of the SEMG during MVC. The H-reflex pathway is involved in the neural plastic changes that occur following spinal manipulation. The improvements in MVC following spinal manipulation are likely attributed to increased descending drive and/or modulation in afferents. Spinal manipulation appears to prevent fatigue developed during maximal contractions. Spinal manipulation appears to alter the net excitability of the low-threshold motor units, increase cortical drive, and prevent fatigue.