<p>Accurate modelling of knee joint biomechanics is essential for understanding ligament function, joint degeneration, and musculoskeletal (MSK) adaptations. However, conventional MSK models often oversimplify the knee as a rigid joint and neglect the three-dimensional (3D) interactions between the anterior and posterior cruciate ligaments (ACL and PCL). In this study, a novel finite element (FE) MSK model of the lower extremity was developed and validated. The model incorporated detailed 3D geometries and contact definitions for cartilage, menisci, and ligaments, enabling simultaneous estimation of muscle forces, joint kinematics, and tissue contact stresses under dynamic loading conditions. Model predictions indicated good agreement with experimental data for cartilage and ligament mechanics, joint axial contact forces, muscle forces, and kinematics. The model revealed that ACL–PCL contact was both activity- and phase-dependent, occurring during walking, stair ascent, and stand-to-sit movements, with peak contact pressure reaching 0.32&#xa0;MPa during stand-to-sit. Although this contact had limited effects on overall joint loading, it markedly influenced tibial internal–external rotation, highlighting its biomechanical relevance. Furthermore, the model identified distinct gait-specific loading patterns: the ACL was the primary load-bearing ligament during walking, whereas the PCL was dominant during stair ascent and stand-to-sit. These findings underscore the importance of incorporating cruciate ligament contact mechanics in MSK modelling to accurately capture dynamic knee function. The proposed FE MSK model provides a robust platform for analyzing cruciate ligament behaviour and load-sharing mechanisms during functional activities, with applications in orthopedic research, injury prevention, rehabilitation, and surgical planning.</p>