Wall stress (WS) is associated with high arterial pressure and affects the localization of atherosclerotic lesions. We sought to non-invasively investigate the distribution of WS along the length of human coronary arteries and investigate its potential effect on atherosclerosis in association with vascular stiffness, local arterial curvature and plaque volume. We reconstructed three-dimensionally 28 coronary arteries from 22 subjects who had undergone coronary computed tomography angiography. Coronary arteries were divided in 2 mm-long segments. WS, vascular stiffness, plaque volume and curvature were calculated in each segment using computational fluid dynamics and morphology measurements. Plaque segments exhibited lower WS compared to their adjacent normal segments. Within plaques, WS was lower in the mid plaque portion compared to the upstream portion. Plaque volume was higher in the mid plaque portion compared to upstream and downstream portions. Low WS was associated with high curvature and both low WS and high curvature were associated with increased plaque volume. The current study demonstrates that WS and plaque volume are not uniform in the longitudinal axis of human coronary plaque. Calculation of WS could serve as a surrogate for the localization of plaque development and the identification of plaques at a more advanced stage of progression.