A crucial step in understanding the onset and progression of cartilaginous disease, such as osteoarthritis, is to study how cartilage mechanics and composition relate in response to controlled loading in disease-free joints. Both knees of 10 healthy participants were imaged with a 3 T magnetic resonance imaging (MRI) scanner at two timepoints (7 ± 3 days apart). Quantitative MR images for T1ρ and T2* were acquired with the knee in two states:​ i) a traditional setup without load applied, and ii) while a loading device applied a 40% bodyweight load to the plantar aspect of the foot. Associations between mechanical metrics (cartilage deformation, cartilage strain, change in bone-bone distance, and change in cartilage contact area) and compositional metrics (T1ρ and T2* relaxation times) were identified. Significant decreases in bone-bone distance were seen in all compartments in response to load. Articular cartilage thickness consistently decreased, but differences were significant for only half of the medial and lateral compartments in the tibia and femur. Strains ranged from 4.9% in compression to 0.3% in tension. No significant changes were found in cartilage contact area. T1ρ and T2* relaxation times changed significantly with the application of load, with the femoral and tibial cartilage exhibiting opposite responses. No significant associations were observed between mechanical and compositional metrics for T1ρ scans, but T2* scans had three significant relationships. Results from this work demonstrate that loading can induce tibiofemoral articular cartilage composition changes, as assessed with T1ρ and T2*, even with small magnitude measurements of mechanics.