Brain activations underlying cognitive processes are subject to modulation as a result of increasing cognitive demands, individual differences, and practice. The present study investigated these modulatory effects in a cognitive control task which required inhibition of prepotent responses based on the contents of working memory (WM) and which enabled a novel dissociation of item-specific and task-skill effects resulting from brief practice. Distinct responses in areas underlying WM and inhibitory control in the absence of behavioral changes reflected different effects of item repetition and general task practice on tonic working memory and phasic inhibitory processes. Item repetition was associated with decreases in both unique and common areas subserving WM and inhibitory control. In contrast, general task practice was reflected in decreases in the level of tonic WM activity required to maintain a consistently high level of task performance but increased activity in a number of core inhibitory regions including dorsolateral and inferior PFC and inferior parietal cortex. Furthermore, both practice and individual differences in task performance were associated with the ability to modulate and maintain activity in frontostriatal areas mediating attentional control, suggesting that the areas that differ between individuals can be modulated by practice within an individual. These results raise the possibility that a fundamental human ability, reflexive cognitive control, is amenable to practice.