This paper deals with a computational fluid dynamics (CFD) and experimental drag analysis on an isolated rotating wheel subsystem (including its accessories: tire, suspension, A-arms, and fender) of a motor tricycle vehicle with two wheels in front. The main goal of the present work is to study the effect of the fender on the wheel subsystem drag and its optimization. The Star CCM+ commercial code was used for the numerical simulations. Different flow conditions were simulated and some results were validated by comparison to wind tunnel experimental results. To perform drag optimization, several aerodynamic fender shapes were designed and simulated as part of the subsystem. A drastic drag reduction up to 30.6% compared to the original wheel subsystem was achieved through numerical simulations.