To fully understand TMJ cartilage degeneration and appropriate repair mechanisms, it is critical to understand the native structure-mechanics relationships of TMJ cartilage and any local variation that may occur in the tissue. Here, we used confocal elastography and digital image correlation to measure the depth-dependent shear properties as well as the structural properties of TMJ cartilage at different anatomic locations on the condyle to identify depth-dependent changes in shear mechanics and structure. We found that samples at every anatomic location showed qualitatively similar shear modulus profiles as a function of depth. In every sample, four distinct zones of mechanical behavior were observed, with shear modulus values spanning 3–5 orders of magnitude across zones. However, quantitative characteristics of shear modulus profiles varied by anatomic location, particularly zone size and location, with the most significant variation in zonal width occurring in the fibrocartilage surface layer (zone 1). This anatomic variation suggests that different locations on the TMJ condyle may play unique mechanical roles in TMJ function. Furthermore, zones identified in the mechanical data corresponded on a sample-by-sample basis to zones identified in the structural data, indicating the known structural zones of TMJ cartilage may also play unique mechanical roles in TMJ function. © 2021