In the past it has often been assumed that the cortical networks for visually guided movement are the same for males and females. Here we use functional magnetic resonance imaging (fMRI) to show significant sex-related differences in human brain activity during visual-to-motor transformation tasks. Although the behavioural performance of the male and female groups did not differ, sex-related differences in levels of blood oxygen level-dependent fMRI activity are apparent in several cortical areas that have previously been demonstrated to be important for visually guided movements. These areas include the primary sensorimotor, dorsal premotor, superior parietal and lateral sulcus regions. Furthermore, the data indicate that the nature of these sex differences depends on the spatial mapping between a visual cue and the motor response that it guides.