How does motivation interact with cognitive control during challenging behavioral conditions? Here, we investigated the interactions between motivation and cognition during a response conflict task and tested a specific model of the effect of reward on cognitive processing. Behaviorally, participants exhibited reduced conflict during the reward versus no-reward condition. Brain imaging results revealed that a group of subcortical and fronto-parietal regions was robustly influenced by reward at cue processing and, importantly, that cue-related responses in fronto-parietal attentional regions were predictive of reduced conflict-related signals in the medial pFC (MPFC)/ACC during the upcoming target phase. Path analysis revealed that the relationship between cue responses in the right intraparietal sulcus (IPS) and interference-related responses in the MPFC during the subsequent target phase was mediated via signals in the left fusiform gyrus, which we linked to distractor-related processing. Finally, reward increased functional connectivity between the right IPS and both bilateral putamen and bilateral nucleus accumbens during the cue phase, a relationship that covaried with across-individual sensitivity to reward in the case of the right nucleus accumbens. Taken together, our findings are consistent with a model in which motivationally salient cues are employed to upregulate top–down control processes that bias the selection of visual information, thereby leading to more efficient stimulus processing during conflict conditions.