Although significant insights into the neural basis of numerical and mathematical processing have been made, the neural processes that enable abstract symbols to become numerical remain largely unexplored in humans. In the present study, adult participants were trained to associate novel symbols with nonsymbolic numerical magnitudes (arrays of dots). Functional magnetic resonance imaging was used to examine the neural correlates of numerical comparison versus recognition of the novel symbols after each of two training stages. A left-lateralized fronto-parietal network, including the intraparietal sulcus, the precuneus, and the dorsal prefrontal cortex, was more active during numerical comparison than during perceptual recognition. In contrast, a network including bilateral temporal–occipital regions was more active during recognition than comparison. A whole-brain three-way interaction revealed that those individuals who had higher scores on a postscan numerical task (measuring their understanding of the global numerical organization of the novel symbols) exhibited increasing segregation between the two tasks in the bilateral intraparietal sulci as a function of increased training. Furthermore, whole-brain regression analysis showed that activity in the left intraparietal sulcus was systematically related to the effect of numerical distance on accuracy. These data provide converging evidence that parietal and left prefrontal cortices are involved in learning to map numerical quantities onto visual symbols. Only the parietal cortex, however, appeared systematically related to the degree to which individuals learned to associate novel symbols with their numerical referents. We conclude that the left parietal cortex, in particular, may play a central role in imbuing visual symbols with numerical meaning.