Purpose <p>While weight management is a primary recommendation for individuals with or at risk of knee osteoarthritis (KOA), the isolated mechanical impact of body-mass reduction on knee joint loads remains incompletely understood. This study aimed to quantify the acute biomechanical responses of peak knee joint loads to simulated body-mass reduction across various daily functional activities.</p> Methods <p>Eleven healthy adults performed level walking, stair ascent, stair descent, stand-to-sit, and sit-to-stand under a simulated overweight baseline and three unloading conditions created by progressively reducing externally added loads using weighted vests and limb straps. Motion data were recorded using a motion capture system, and OpenSim was used to estimate tibiofemoral contact force, patellofemoral contact force, and knee joint moment.</p> Results <p>Simulated body-mass reduction generally reduced peak knee joint loads in a task-dependent manner. Peak tibiofemoral contact force decreased significantly across all tasks (<i>p</i> &lt; 0.05), with pronounced reductions in high-flexion activities. Patellofemoral contact force and knee joint moment also decreased, although responses varied by task and variable. Furthermore, the magnitude of joint load reduction varied across the progressive stages of external unloading.</p> Conclusion <p>The acute mechanical effects of simulated body-mass reduction on knee joint loads vary significantly across different functional tasks and joint compartments. These findings focus on the mechanical contribution of body-mass reduction to knee joint loading, providing quantitative biomechanical evidence to inform load-management strategies for individuals with excessive knee loading.</p>