Epistemic curiosity (EC) is a cornerstone of human cognition that contributes to the actualization of our cognitive potential by stimulating a myriad of information-seeking behaviors. Yet, its fundamental relationship with uncertainty remains poorly understood, which limits our ability to predict within- and between-individual variability in the willingness to acquire knowledge. Here, a two-step stochastic trivia quiz designed to induce curiosity and manipulate answer uncertainty provided behavioral and neural evidence for an integrative model of EC inspired from predictive coding. More precisely, our behavioral data indicated an inverse relationship between average surprise elicited by previous trivia items and EC levels, which depended upon hemodynamic activity in the rostrolateral prefrontal cortex from one trial to another and from one individual to another. Complementary, the relief of acute curiosity recruited the ventral striatum when knowledge delivery was unpredictable. Taken together, our results account for the temporal evolution of EC over time, as well as for the interplay of EC, prior knowledge and surprise in controlling memory gain.