One becomes accustomed to repeated exposures, even for a novel event. In the present study, we investigated how predictability affects habituation to novelty by applying a mathematical model of arousal that we previously developed, and conducted a psychophysiological experiment to test the model prediction. We formalized habituation to novelty as a decrement in Kullback-Leibler divergence from Bayesian prior to posterior (i.e., information gain) representing arousal evoked from a novel event through Bayesian update. The model predicted an interaction effect between initial uncertainty and initial prediction error (i.e., predictability) on habituation to novelty: The greater the initial uncertainty, the faster the information gain decreases (i.e., the sooner one is habituated). Experimental results using subjective reports of surprise and event-related potential (P300) evoked by visual-auditory incongruity supported the model prediction. Our findings suggest that in highly uncertain situations, repeated exposure to stimuli may enhance habituation to novel stimuli.