The aim of this study was to assess the impact of the variability of the Yeoh model when modeling the contact of bones through cartilage in the knee in compression and flexion-extension within a hybrid knee model. Firstly, a Sobol sequence of 64 samples and four variables representing the Yeoh parameters of the cartilage of the femur and tibia was generated. Based on these samples, 2 × 64 finite element contact models of the geometry of the sphere plane were generated and solved for healthy tissue affected by osteoarthritis. The resulting indentation curves were incorporated into a multibody knee joint model. The obtained results suggested that cartilage variability severely affected the knee in compression by up to 32%. However, the same variability also affected the flexion-extension motion, although to a lesser extent, with a relative change to the range of angular displacements of almost 7%. Osteoarthritic tissue was consistently more affected by this variability, suggesting that when modeling degenerated tissue, complex joint models are necessary.