Knowledge of the failure properties of the aorta is essential to understand the mechanisms of dissection and rupture. Limited information is, however, available in humans or experimental animals about the layer-specific properties and their segmental variations have not been determined. In this paper, the failure properties of the intima, media, and adventitia were studied in nine consecutive aortic segments and two principal directions. Detailed biomechanical tests were performed with a tensile-testing device on 756 layer strips, harvested from fourteen cadaveric subjects aged 21–82 years. Intimal and medial strength in either direction remained invariant along the aorta, and their extensibility longitudinally decreased, whereas adventitial strength and extensibility longitudinally increased, explaining why the preferential sites for the development of aortic dissection or traumatic rupture are in the proximal aorta. The media was stronger circumferentially than longitudinally in all segments, accounting for the typically transverse tearing in dissection/rupture. The adventitial properties were significantly higher than the intimal and medial in most segments. Still, the intima had similar strength but lower extensibility compared to the media in both directions, and higher maximum stiffness longitudinally in several segments. The rupture surface of all layers was not perpendicular to the loading axis, more so in the circumferential strips compared to longitudinal ones. Aging impaired the extensibility and strength of all layers, particularly the media, but did not affect the maximum stiffness and rupture-surface direction. Females were rarely associated with different failure properties compared to age-matched males.