Recent studies have challenged the view that orbitofrontal cortex (OFC) and amygdala mediate flexible reward-guided behavior. We trained macaques to perform an object discrimination reversal task during fMRI sessions and identified a lateral OFC (lOFC) region in which activity predicted adaptive win-stay/lose-shift behavior. Amygdala and lOFC activity was more strongly coupled on lose-shift trials. However, lOFC-amygdala coupling was also modulated by the relevance of reward information in a manner consistent with a role in establishing how credit for reward should be assigned. Day-to-day fluctuations in signals and signal coupling were correlated with day-to-day fluctuation in performance. A second experiment confirmed the existence of signals for adaptive stay/shift behavior in lOFC and reflecting irrelevant reward in the amygdala in a probabilistic learning task. Our data demonstrate that OFC and amygdala each make unique contributions to flexible behavior and credit assignment. •Orbitofrontal cortex determines future behavior on the basis of reward feedback•Variation in orbitofrontal cortex activity is correlated with variation in learning•Amygdala carries information about irrelevant reward•Amygdala-orbitofrontal interactions emphasize relevant not irrelevant reward Chau et al. identify a posterior lateral OFC (lOFC) region in which activity predicts adaptive win-stay/lose-shift behavior. Amygdala activity predicts only lose-shift behavior but carries information about irrelevant rewards. lOFC-amygdala connectivity is modulated dynamically by the relevance of reward information.