Speed and accuracy of motor responses to lateralized stimuli are influenced by the spatial overlap between stimulus location and required response. Responses showing high spatial overlap with peripheral cues benefit from a bottom-up driven enhancement of attention to the respective location, whereas low overlap requires top-down modulated reorienting of resources. Here we investigated the interaction between these two processes using a spatial stimulus-response compatibility task. Subjects had to react to lateralized visual stimuli with a button press using either the ipsilateral (congruent condition) or the contralateral (incongruent condition) index finger. Stimulus-driven bottom-up processes were associated with significant contralateral activation in V5, the intraparietal sulcus (IPS) and the premotor cortex (PMC). Incongruent versus congruent responses evoked significant activation in bilateral IPS and PMC, highly overlapping with the activations found for stimulus-driven bottom-up processes, as well as additional activation in bilateral anterior insula and right dorsolateral prefrontal cortex (DLPFC) and temporoparietal junction (TPJ). Moreover, a region anterior to the bottom-up driven activation in the IPS was associated with top-down modulated directionality-specific reorienting of motor attention during incongruent motor responses. Based on these results, we propose that stimulus-driven activation of contralateral IPS and PMC represent key neuronal substrates for the behavioral advantage observed when reacting toward a congruently lateralized stimulus. Additional activation in bilateral insula and right DLPFC and TPJ during incongruent responses should reflect top-down control mechanisms mediating contextual (i.e., task) demands. Furthermore, this study provides evidence for both overlapping and disparate substrates of bottom-up and top-down modulated attentional processes in the IPS.