The prefrontal cortex (PFC) is assumed to contribute to goal-directed episodic encoding by exerting cognitive control on medial temporal lobe (MTL) memory processes. However, it is thus far unclear to what extent the contribution of PFC-MTL interactions to memory manifests at a structural anatomical level. We combined functional magnetic resonance imaging and fiber tracking based on diffusion tensor imaging in 28 young, healthy adults to quantify the density of white matter tracts between PFC regions that were activated during the encoding period of a verbal free-recall task and MTL subregions. Across the cohort, the strength of fiber bundles linking activated ventrolateral PFC regions and the rhinal cortex (comprising the peri- and entorhinal cortices) of the MTL correlated positively with free-recall performance. These direct white matter connections provide a basis through which activated regions in the PFC can interact with the MTL and contribute to interindividual differences in human episodic memory.