The right inferior frontal gyrus is generally considered a critical region for motor response inhibition. Recent studies, however, suggest that the role of this cortical area in response inhibition may be overstated and that the contributions of other aspects of the prefrontal cortex are often overlooked. The current study used optical imaging to identify regions of the prefrontal cortex beyond the right inferior frontal gyrus which may serve to support motor response inhibition. Forty-three right-handed healthy adults completed a manual Go/No-Go task while evoked oxygenation of the prefrontal cortex was measured using 16-channel functional near-infrared spectroscopy. During motor response inhibition, the right inferior frontal gyrus, and to a lesser extent the homologous contralateral region, showed increased activation relative to a baseline task. Conversely, the medial prefrontal cortex was significantly deactivated, and the extent of reduced activity in this region was associated with fewer errors on the response inhibition task. These findings suggest a more substantial role of the left inferior frontal gyrus in response inhibition and possibly a distinct function of the middle frontal gyrus subserving error detection on manual motor control tasks.