Osteoarthritis is a degenerative joint disease that progressively impairs the biomechanical functionality of articular cartilage. Although it is typically diagnosed during its advanced stages, subtle biomechanical changes emerge much earlier, preceding any observable morphological damage. Therefore, this study investigates these early-stage biomechanical changes. Cartilage samples were extracted from the bovine femoral head and then subjected to 0.05% trypsin treatment to mimic progressive degradation. The elastic modulus and permeability were determined by integrating the indentation experimental data and finite element analysis. The results demonstrated a marked decline in the elastic modulus, decreasing by 78% from 1.89 MPa to 0.42 MPa. Conversely, permeability significantly increased by 201%, rising from 1.34 × 10−15 m4/Ns to 4.03 × 10−15 m4/Ns. The outcomes enhance understanding of the biomechanical changes associated with early osteoarthritis and offer valuable insights for developing quantitative diagnostic tools for early-stage detection.