Mastering single-digit arithmetic during school years is commonly thought to depend upon an increasing reliance on verbally memorized facts. An alternative model, however, posits that fluency in single-digit arithmetic might also be achieved via the increasing use of efficient calculation procedures. To test between these hypotheses, we used a cross-sectional design to measure the neural activity associated with single-digit subtraction and multiplication in 34 children from 2nd to 7th grade. The neural correlates of language and numerical processing were also identified in each child via localizer scans. Although multiplication and subtraction were undistinguishable in terms of behavior, we found a striking developmental dissociation in their neural correlates. First, we observed grade-related increases of activity for multiplication, but not for subtraction, in a language-related region of the left temporal cortex. Second, we found grade-related increases of activity for subtraction, but not for multiplication, in a region of the right parietal cortex involved in the procedural manipulation of numerical quantities. The present results suggest that fluency in simple arithmetic in children may be achieved by both increasing reliance on verbal retrieval and by greater use of efficient quantity-based procedures, depending on the operation.