The mechanical and structural behavior of the aorta depend on physiological functions and vary from proximal to distal. Understanding the relation between regionally varying mechanical and multi-scale structural response of aorta can be helpful to assess the disease outcomes. Therefore, this study investigated the variation in mechanical and multi-scale structural properties among the major segments of aorta such as ascending aorta (AA), descending aorta (DA) and abdominal aorta (ABA), and established a relation between mechanical and multi-structural parameters. The obtained results showed significant increase in anisotropy and nonlinearity from proximal to distal aorta. The change in periphery length and radii between load and stress free configuration was also found increasing far from the heart. Opening angle was significantly large for ABA than AA and DA (AA/DA vs ABA; p = 0.001). Mean circumferential residual stretch (ratio of mean periphery length at load and stress free configurations) was found decreasing between AA and DA, and then increasing between DA to ABA and its value was significantly more for ABA (AA vs DA; p = 0.041, AA vs ABA; p = 0.001, DA vs ABA; p = 0.001). The waviness of collagen fibers, collagen fiber content, collagen fibril diameter and total protein content were found significantly increasing from proximal to distal. Pearson correlation test showed a significant linear correlation between variation in mechanical and multi-scale structural parameters over the aortic length. Residual stretch was found positively correlated with collagen fiber content (r = 0.82) whereas opening angel was found positively correlated with total protein content (TPC) (r = 0.76).