The present study focuses on investigating the aerodynamic interaction between a three-element wing and wheel in ground effect, following the Formula One regulation change set for 2022, among which is the simplification of the front wing. This was accomplished by conducting a three-dimensional computational fluid dynamics analysis, using a Detached-Eddy Simulation approach, on a simplified one-quarter model of a Formula One racing car. The main goal was to examine how changing the front wing pressure distribution, by changing the incidence of the second flap, affected the wheel wake. The flow investigation indicated that the wheel wake is influenced by the flap configuration, which is mainly due to the fact that different flap configurations produce different upwash flow fields, leading to a variation of the separation point on top of the tire. As the separation point moves rearwards, the downwash generated in the central region (for a vertical plane) of the wheel wake increases incrementally, leading to a resultant wake that is shorter and further apart. The force investigation showed that the proximity between the region of instability (i.e., vortex breakdown) and the wing’s trailing edge influences the behavior of the transient oscillations, regarding the forces acting on the wing: detecting higher drag force fluctuations, when compared to downforce fluctuations.