Prepulse inhibition (PPI) refers to the process wherein startle responses to salient stimuli (e.g., startling sound pulses) are attenuated by the presentation of another stimulus (e.g., a brief pre-pulse) immediately before the startling stimulus. Accordingly, deficits in PPI reflect atypical sensorimotor gating that is linked to neurobehavioral systems underlying responsivity to emotionally evocative cues. Little is known about the effects of changes in visual contextual information in PPI among humans. In this study, the effects of introducing unexpected changes in the visual scenes presented on a computer monitor on the human auditory startle response and PPI were assessed in young adults. Based on our animal data showing that unexpected transitions from a dark to a light environment reduce the startle response and PPI in rats after the illumination transition, it was hypothesized that novel changes in visual scenes would produce similar effects in humans. Results show that PPI decreased when elements were added to or removed from visual scenes, and that this effect declined after repeated presentations of the modified scene, supporting the interpretation that the PPI reduction was due to novel information being processed. These findings are the first to demonstrate that novel visual stimuli can impair sensorimotor gating of auditory stimuli in humans.