Contextual information plays a critical role in daily life, helping define episodic experience and facilitating the retrieval of goal-relevant memories. Moreover, memory retrieval underlies mental simulation and the planning of future behavior. The hippocampus and neighboring medial temporal lobe (MTL) cortices are believed to play a critical role in the flexible representation and context-guided retrieval of the unique features of past experiences. I will present a series of experiments in which I combine immersive virtual navigation paradigms with univariate and multivariate functional magnetic resonance imaging (fMRI) techniques to study the MTL mechanisms governing context-guided memory and planning. First, I will discuss foundational work, motivated by computational models of memory, that links human hippocampal mechanisms to the learning and flexible retrieval of sequential navigational experiences. I will then present high-resolution fMRI data that link hippocampal mechanisms to prospective retrieval and the simulation of future experience. Using multivoxel pattern decoding techniques, my data provide novel evidence that the human MTL supports goal-directed navigation by representing future goal states during navigational planning. Convergent evidence from these studies reveals mechanistic links between network-level interactions of the hippocampus and the translation of memory traces into goal-directed planning and action. Collectively, these findings provide a core framework for understanding, and programmatic research into, the neural mechanisms that enable humans to distinguish between memories, generalize across experiences, and leverage memory traces to guide planning and behavior.