Low wall shear stress (WSS) is implicated in endothelial dysfunction and atherogenesis. The accumulation of macromolecules is also considered as an important factor contributing to the development of atherosclerosis. In the present study, a fluid-wall single-layered model incorporated with shear-dependent transport parameters was used to investigate albumin and low-density lipoprotein (LDL) transport in an in vivo computed tomographic image-based human right coronary artery (RCA). In the fluid-wall model, the bulk blood flow was modeled by the Navier–Stokes equations, Darcy’s law was employed to model the transmural flow in the arterial wall, mass balance of albumin and LDL was governed by the convection-diffusion mechanism with an additional reaction term in the wall, and the Kedem–Katchalsky equations were applied at the endothelium as the interface condition between the lumen and wall. Shear-dependent models for hydraulic conductivity and albumin permeability were derived from experimental data in literature to investigate the influence of WSS on macromolecular accumulation in the arterial wall. A previously developed so-called lumen-free time-averaged scheme was used to approximate macromolecular transport under pulsatile flow conditions. LDL and albumin accumulations in the subendothelial layer were found to be colocalized with low WSS. Two distinct mechanisms responsible for the localized accumulation were identified: one was insufficient efflux from the subendothelial layer to outer wall layers caused by a weaker transmural flow; the other was excessive influx to the subendothelial layer from the lumen caused by a higher permeability of the endothelium. The comparison between steady flow and pulsatile flow results showed that the dynamic behavior of the pulsatile flow could induce a wider and more diffuse macromolecular accumulation pattern through the nonlinear shear-dependent transport properties. Therefore, it is vital to consider blood pulsatility when modeling the shear-dependent macromolecular transport in large arteries. In the present study, LDL and albumin accumulations were observed in the low WSS regions of a human RCA using a fluid-wall mass transport model. It was also found that steady flow simulation could overestimate the magnitude and underestimate the area of accumulations. The association between low WSS and accumulation of macromolecules leading to atherosclerosis may be mediated through effects on transport properties and mass transport and is also influenced by flow pulsatility.