This fMRI study investigated the neural correlates of reward-related trial-and-error learning in association with changing degrees of stimulus-outcome predictabilities. We found that decreasing predictability was associated with increasing activation in a frontoparietal network. Only maximum predictability was associated with signal decreases across the learning process. The receipt of monetary reward revealed activation in the striatum and associated frontoparietal regions. Present data indicate that during reward-related learning, high uncertainty forces areas relevant for cognitive control to remain activated. In contrast, learning on the basis of predictable stimulus-outcome associations enables the brain to reduce resources in association with the processes of prediction.