The mechanical properties and microstructure of articular cartilage from the canine tibial plateau were studied 12 weeks after total medial meniscectomy. The organization of the birefringent collagen network was measured with quantitative polarized light microscopy to determine the thickness and the degree of organization of the superficial and deep zones. The zonal concentration of sulfated glycosaminoglycan was quantified with digital densitometry of safranin-O staining. Equilibrium compressive and shear properties, as well as dynamic shear properties, were measured at sites adjacent to those of microstructural analysis. The results evinced significant loss of cartilage function following meniscectomy, with decreases of 20–50% in the compressive and shear moduli. There was no evidence of alterations in the degree of collagen fibrillar organization, although a complete loss of the surface zone was seen in 60% of the samples that underwent meniscectomy. Meniscectomy resulted in a decreased concentration of sulfated glycosaminoglycan, and significant positive correlations were found between the equilibrium compressive modulus and the glycosaminoglycan content. Furthermore, the shear properties of cartilage correlated directly with collagen fibrillar organization measured at the superficial zone of corresponding sites. These findings demonstrate that meniscectomy leads to impaired mechanical function of articular cartilage, with significant evidence of quantitative correlations between cartilage microstructure and mechanics.