This study determined the load- and limb-dependent neuromuscular responses to fatiguing, bilateral, leg extension exercise performed at a moderate (50% one-repetition maximum [1RM]) and high load (80% 1RM). Twelve subjects completed 1RM testing for the bilateral leg extension, followed by repetitions to failure at 50% and 80% 1RM, on separate days. During all visits, the electromyographic (EMG) and mechanomyographic (MMG), amplitude (AMP) and mean power frequency (MPF) signals were recorded from the vastus lateralis of both limbs. There were no limb-dependent responses for any of the neuromuscular signals and no load-dependent responses for EMG AMP, MMG AMP, or MMG MPF (p = .301–.757), but there were main effects for time that indicated increases in EMG and MMG AMP and decreases in MMG MPF. There was a load-dependent decrease in EMG MPF over time (p = .032) that suggested variability in the mechanism responsible for metabolite accumulation at moderate versus high loads. These findings suggested that common drive from the central nervous system was used to modulate force during bilateral leg extension performed at moderate and high loads.