A certain degree of varus alignment is physiological in the native knee, and alignment strategies such as kinematic and functional alignment permit residual postoperative varus. However, identical total varus angles may result from varying combinations of femoral and tibial varus, whose biomechanical implications for implant loading and ligament stress remain unclear. This study aims to investigate the biomechanical effects of different femoral–tibial varus configurations in total knee arthroplasty (TKA). Using combined geometric modeling and finite element analysis, TKA models with different varus combinations were constructed to evaluate changes in limb moment arms, polyethylene insert stress, and ligament forces during static knee flexion (0°–90°). Results demonstrated that a higher proportion of femoral varus, under equivalent total varus and flexion angles, led to reduced maximum polyethylene stress and decreased tension in the medial collateral ligament (MCL) and anterolateral ligament complex (ALL). Knee flexion angle had a more significant impact on polyethylene stress than varus: stress increased by approximately 2.48 times at 90° flexion compared to 0°, whereas 12° varus increased stress by only approximately 14%. The ALL experienced the greatest tensile load during flexion, indicating a key stabilizing role. In conclusion, optimizing the combination of femoral and tibial varus may help redistribute loads and improve implant longevity. This study reveals, from a biomechanical perspective, how different varus configurations affect stress distribution in the prosthesis and surrounding soft tissues, suggesting that intraoperative osteotomy strategies should comprehensively consider the combined alignment of the femur and tibia.