The levitation tricompartment offloader (TCO) brace is designed to unload all three knee compartments by reducing compressive forces caused by muscle contraction. This study aimed to determine the effect of the TCO on knee contact forces and quadriceps muscle activity in individuals with knee osteoarthritis. Lower limb kinematics, kinetics, and electromyography data were collected during a chair rise-and-lower task. A three-dimensional inverse dynamics model of the lower leg and foot was used with a sagittal plane knee model to compute knee joint forces. TCO brace use significantly decreased forces in the tibiofemoral [p = 0.001;​ mean difference, MD (97.5% confidence interval, CI) −0.62 (−0.91, −0.33) body weight (BW)] and patellofemoral [p = 0.001;​ MD (97.5% CI) −0.88 (−1.36, −0.39) BW] compartments in high-power mode. Significant reductions in quadriceps tendon force [p = 0.002;​ MD (97.5% CI) −0.53 (−0.83, −0.23) BW] and electromyography intensity of the vastus medialis [p = 0.018, MD (97.5% CI) −30.7 (−59.1, −2.3)] and vastus lateralis [p = 0.012, MD (97.5% CI) −26.2 (−48.5, −3.9)] were also observed. The TCO significantly reduced tibiofemoral and patellofemoral contact forces throughout chair lower, and when knee flexion was greater than 50° during chair rise in high power. These results demonstrate that the TCO reduces contact forces in the tibiofemoral and patellofemoral joint compartments and confirms that the TCO unloads the joint by reducing compressive forces caused by the quadriceps. Clinical significance:​ The magnitude of knee joint unloading provided by the TCO is similar to that achieved by clinically recommended levels of bodyweight loss and is therefore expected to result in clinical benefits for knee osteoarthritis patients.