Successful avoidance of predators is critical for animal survival. However, little is known of how predator-attack experience may affect predator-defense behavior. Here, we caught mice by their tails to simulate a predator attack. We found that this led to a quicker flight response to visual threatening cues in experiences mice compared to naive mice. A single predator attack did not induce anxiety but increased activity in brain nuclei related to innate fear and learning. Predator-attack induced quickening of flight was partly rescued by pharmacological blockade of protein synthesis which is critical for learning. Experienced mice significantly reduced focused exploration of the floor during environmental exploration, which may facilitate the discovery of predators. These results suggest that mice can learn from experience of predator attacks to optimize their behavioral patterns for immediate detection of predator cues and a heightened response to these cues, thereby increasing the probability of survival.

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