Driving is a complex behavior that requires the integration of multiple cognitive functions. While many studies have investigated brain activity related to driving simulation under distinct conditions, little is known about the brain morphological and functional architecture in professional competitive driving, which requires exceptional motor and navigational skills. Here, 11 professional racing-car drivers and 11 "naïve" volunteers underwent both structural and functional brain magnetic resonance imaging (MRI) scans. Subjects were presented with short movies depicting a Formula One car racing in four different official circuits. Brain activity was assessed in terms of regional response, using an Inter-Subject Correlation (ISC) approach, and regional interactions by mean of functional connectivity. In addition, voxel-based morphometry (VBM) was used to identify specific structural differences between the two groups and potential interactions with functional differences detected by the ISC analysis. Relative to non-experienced drivers, professional drivers showed a more consistent recruitment of motor control and spatial navigation devoted areas, including premotor/motor cortex, striatum, anterior, and posterior cingulate cortex and retrosplenial cortex, precuneus, middle temporal cortex, and parahippocampus. Moreover, some of these brain regions, including the retrosplenial cortex, also had an increased gray matter density in professional car drivers. Furthermore, the retrosplenial cortex, which has been previously associated with the storage of observer-independent spatial maps, revealed a specific correlation with the individual driver's success in official competitions. These findings indicate that the brain functional and structural organization in highly trained racing-car drivers differs from that of subjects with an ordinary driving experience, suggesting that specific anatomo-functional changes may subtend the attainment of exceptional driving performance.