This fMRI study aimed at unraveling the neural basis of learning alphabet arithmetic facts, as a proxy of the transition from slow and effortful procedural counting-based processing to fast and effortless processing as it occurs in learning addition arithmetic facts. Neural changes were tracked while participants solved alphabet arithmetic problems in a verification task (e.g., F + 4 = J). Problems were repeated across four learning blocks. Two neural networks with opposed learning-related changes were identified. Activity in a network consisting of basal ganglia and parieto-frontal areas decreased with learning, which is in line with a reduction of the involvement of procedure-based processing. Conversely, activity in a network involving the left angular gyrus and, to a lesser extent, the hippocampus gradually increases with learning, evidencing the gradual involvement of retrieval-based processing. Connectivity analyses gave insight in the functional relationship between the two networks. Despite the opposing learning-related trajectories, it was found that both networks become more integrated. Taking alphabet arithmetic as a proxy for learning arithmetic, the present results have implications for current theories of learning arithmetic facts and can give direction to future developments.