Mechanical analysis of articular cartilage is best accomplished via integrative approaches combining multi-modal imaging, mechanical experiments, and mathematical modeling. Healthy cartilage is a load-bearing and lubricating tissue lining the bony ends in diarthrodial joints. Unfortunately, degenerative processes like osteoarthritis lead to progressive damage and ultimately to complete destruction of cartilage, in part through mechanics-mediated mechanisms. We aim to describe the synergy of imaging and modeling to measure and characterize the structural and material properties of cartilage, including tissue morphology, shape, and estimates of intra-tissue distributions of strain and stress. Displacement-encoded MRI and fiber-reinforced constitutive models emerge as excellent approaches for direct measurement and estimation of the mechanics, e.g. displacements and stresses, respectively, within the tissue. We review the application of these approaches for the study of healthy and degenerated cartilage, and challenges that arise when extending these approaches to investigate chondrocyte signaling at the single cell level.