Estimation of the knee joint strength by maximum voluntary isometric contraction (MVIC) is a common practice to assess strength, coordination, safety to return to work or engage in sports after an injury, and to evaluate the efficacy of treatment modalities and rehabilitation strategies. In this study, we utilize a previously validated coupled finite element‐musculoskeletal model of the lower extremity to explore the sensitivity of output measures (posterior cruciate ligament [PCL]/muscle/contact forces and passive moments) in knee MVIC flexion exercises at seated position. To do so, at three knee flexion angles (KFA), input measures (resistance moment and contribution moments of quadriceps and gastrocnemii) were varied at four levels each using the Taguchi design of experiment. Our findings reveal significant increases in PCL forces with KFA (p < 0.01), net MVIC moment (p < 0.01), and resistance moment of quadriceps (p < 0.01). In contrast, they drop at larger activity in gastrocnemii (p < 0.01). Tibiofemoral (TF) contact forces increase with the net MVIC moment (p < 0.01). The passive knee flexion moment, while highly dependent on the location at which computed, also increases with the net MVIC moment (p < 0.01). Changes in KFA, MVIC moment, and proportions thereof carried by quadriceps and/or gastrocnemii substantially affect biomechanics of the joint. Compared with level walking and stair ascent, slightly larger contact forces/stresses and much greater PCL forces are computed. This study improves our understanding of the knee joint behavior during MVIC in effective evaluation and rehabilitation interventions. Besides, it emphasizes the importance of positioning the joint center in model studies.