Knee extension is always performed with coordinated contractions of multiple quadriceps muscle components; however, how the load is shared among them under normal and pathological conditions is unclear. We hypothesized that: the absolute moment generated by each quadriceps component increases with the total knee extension moment; the relative contribution and its dependence on the total knee extension moment are different for different quadriceps components; and the centrally located large vastus intermedius (VI) is favored by the central nervous system at low levels of activation. Electrical stimulation was used to activate each quadriceps component selectively in six human subjects. The relationship between the knee extension moment generated by an individual quadriceps component and the corresponding compound muscular action potential (M-wave) over various contraction levels was established for each quadriceps component. This relationship was used to calibrate the corresponding EMG signal and determine load sharing among quadriceps components during submaximal isometric voluntary knee extension. The VI contributed the most (51.8-39.6%) and vastus medialis the least (9.5-12.2%) to knee extension moment (P<0.05). As the knee extension moment increased, the relative contribution of the VI decreased (P=0.017) while the relation contribution of the vastus lateralis and medialis increased (P</=0.012). The absolute moment generated by each quadriceps component always increased with the total knee extension moment (P<0.002). Our in vivo approach determined subject- and condition-specific load sharing among individual muscles and showed that the central nervous system utilized the centrally located, uniarticular VI in submaximal isometric knee extension.