The aim of this study was to identify which neural substrates are engaged during manual Stroop task performance and compare the activation between 8 late proficient Macedonian-English bilinguals and 10 matched English monolinguals. During functional magnetic resonance imaging (fMRI) adult participants performed four Stroop task conditions in a block design (control, congruent, semantically incongruent, response incongruent). Here we focussed on differences in activation between the two groups in two contrasts: (1) the presence of task-irrelevant information that conflicts at both the response and semantic level (response incongruent versus congruent; interference); and (2) the presence of competing task-relevant information that conflicts at the response level only (response incongruent versus semantically incongruent; response conflict). For the first contrast, comparisons between monolinguals (English) and the first language of bilinguals (Macedonian) revealed greater activation in the posterior regions of monolinguals, possibly indicative of a more elaborate stimulus evaluation process. For the second contrast, bilinguals showed less activation in anterior cingulate and prefrontal regions than monolinguals. As poor performance on the Stroop task has been found to be associated with greater activation in these two regions, we interpret this in light of earlier ideas regarding cognitive control and the advantages of bilingualism. That is, less effortful word-form processing might indicate that bilinguals are more effectively dealing with response conflict. Together the current findings suggest that learning two languages may modify the neural substrates engaged during tasks that rely on executive functioning.