A single exposure to an object can produce long-lasting behavioral change. Here, using event-related functional magnetic resonance imaging (fMRI), we provide evidence for long-lasting changes in cortical activity associated with perceiving and naming objects. In posterior regions, we observed an immediate (30-second) and long-lasting (3-day) decrease in neural activity after brief (200-ms) exposure to nameable and nonsense objects. In addition, slower-developing decreases in left inferior frontal activity were observed concurrently with increases in left insula activity, only for nameable objects. These time-dependent cortical changes may reflect two distinct learning mechanisms: the formation of sparser, yet more object-form-specific, representations in posterior regions, and experience-induced reorganization of the brain circuitry underlying lexical retrieval in anterior regions.