The carotid artery is one of the most favorable locations for atherosclerotic plaque accumulation due to its unique geometry. It predominantly occurs at the outer wall of the internal carotid artery (ICA) near the carotid sinus. Fluid–structure interaction study of hemodynamics in the carotid artery with a focus on carotid sinus plays a prominent role in explaining the development and progression of the atherosclerotic lesion. In this study, hemodynamic parameters affecting the plaque accumulation in the carotid artery were investigated with a focus on the carotid sinus. An idealized carotid artery model was taken and hemodynamic parameters such as deformation, wall shear stress (WSS), oscillatory shear index (OSI), relative residence time (RRT), and Helicity were investigated. The atherosclerosis-prone carotid sinus region had significantly low WSS, and low helicity resulting in higher OSI. In these regions, the flow separation had decreased the velocity significantly with a high-velocity angle. The flow divider had significantly elevated WSS due to a higher pressure gradient. Stenosis is predicted to occur at the downstream area of the carotid sinus and develop downstream due to flow separation leading to endothelial dysfunction. Decreased vascular WSS, helicity, and higher OSI are key to the development of endothelial dysfunction leading to atherosclerotic lesion in the carotid sinus.