Comparing and contrasting motor unit recruitment and activation for the same muscles for multiple versus single-joint exercise may provide a better understanding of neuromuscular fatigue. The purpose of this study, therefore, is to compare the slope and y-intercept terms for the three superficial quadriceps femoris (vastus lateralis, rectus femoris, and vastus medialis) muscles derived from the log-transformed EMG amplitude-power output relationship between the single-leg knee-extensor ergometry and the single-leg cycle ergometry. Ten healthy college-aged men who engaged in regular physical activity visited the laboratory on two occasions separated by seven days to perform either single-leg cycle ergometry (CE) or single-leg knee-extensor ergometry (KE) in a randomized order. For each visit, subjects performed incremental exercise until voluntary fatigue. EMG electrodes were placed on the superficial quadriceps femoris muscles. The slope and y-intercept terms, for each muscle, for the EMG amplitude versus power output relationship was examined using the log-transformed model for each subject’s data. The results indicated no significant (p > 0.05) mean differences for either slope or y-intercept terms between exercise modes and across muscles. In addition, separate repeated measures ANOVAs were used to determine mean differences for the slope and y-intercept values between the three muscles. In addition, separate 2 [mode: CE or KE] × intensity [intensity: 30, 60, and 90% of maximal workload] repeated measures ANOVAs were conducted for each muscle. There was a significant (p < 0.05) mode × exercise intensity interaction for each muscle. Follow-up testing indicated that in the most cases, the normalized EMG amplitude was significantly higher for single-leg knee-extensor ergometry than single-leg cycle ergometry. These results indicated that incremental single-leg knee-extensor ergometry activates the superficial quadriceps femoris muscles significantly greater than single-leg cycle ergometry.