The search for high aerodynamic performance of a race car is one of the main aspects of the design process. The flow around the basic body shape is complicated by the presence of the rotating wheels. This is especially true in race cars on which the wheels are not shrouded, where the effects on the flow field are considerable. Despite this, few works have focused on the flow around the rotating wheels. In this paper, CFD techniques were used to provide a detailed analysis of the flow structures generated by the interaction between a multielement inverted wing and the wheel of an open-wheel race car. In the first part, the CFD approach was validated for the isolated wheel case by comparing the results with experimental and numerical data from the literature. The wheel was analyzed both in stationary and unsteady flow conditions. Then, the CFD model was adopted to study the interaction of the flow structures between the wheel with the real grooves on the tire and the front wing of a Formula 1 car. Three different configurations were considered in order to differentiate the individual effects. The discussions were supported by the values of the aerodynamic performance coefficients and flow contours.