How are rules used to transfer knowledge to new stimuli? We used a complex rule learning and transfer task to identify neural systems underlying rule learning, application, and transfer to novel stimuli. We used functional MRI Constrained Principal Components Analysis (fMRI-CPCA) to identify neural systems active during each phase. Two networks were associated with rule transfer. First, a rostral prefrontal network that was recruited during rule transfer with higher activity for more complex rules. This network is consistent with previous research finding that the rostral prefrontal cortex is necessary for abstract and hierarchical rule learning, relational integration, and analogical mapping in human reasoning. Second, a ventromedial prefrontal-hippocampal network that began to be recruited during rule application and increased in activity across the rule transfer phase with greater activity for more difficult rules. This pattern indicates a role in applying rules regardless of stimulus familiarity, as well as sensitivity to the difficulty of the transfer. These results are consistent with previous research establishing the role of the VMPFC-hippocampal network in forming and applying memory schemas via processes of schema reinstatement. Frontoparietal systems associated with the dorsal attention and salience networks were recruited primarily during rule learning and decreased in activity in the later stages of the task. Overall, the results indicate that rule learning and rule transfer differ qualitatively and that additional memory and executive function networks are utilized during transfer to support the cognitive demands necessary to generalize knowledge to new stimuli and integrate sources of information to make a decision.