In generative models of brain function, internal representations are used to generate predictions of sensory input, yet little is known about how internal models influence sensory processing. Here we show that, with experience in a virtual environment, the activity of neurons in layer 2/3 of mouse primary visual cortex (V1) becomes increasingly informative of spatial location. We found that a subset of V1 neurons exhibited responses that were predictive of the upcoming visual stimulus in a spatially dependent manner and that the omission of an expected stimulus drove strong responses in V1. Stimulus-predictive responses also emerged in V1-projecting anterior cingulate cortex axons, suggesting that anterior cingulate cortex serves as a source of predictions of visual input to V1. These findings are consistent with the hypothesis that visual cortex forms an internal representation of the visual scene based on spatial location and compares this representation with feed-forward visual input.