Current models of visual perception suggest that during scene categorization, low spatial frequencies (LSF) are processed rapidly and activate plausible interpretations of visual input. This coarse analysis would then be used to guide subsequent processing of high spatial frequencies (HSF). The present fMRI study examined how processing of LSF may influence that of HSF by investigating the neural bases of the semantic interference effect. We used hybrid scenes as stimuli by combining LSF and HSF from two different scenes, and participants had to categorize the HSF scene. Categorization was impaired when LSF and HSF scenes were semantically dissimilar, suggesting that the LSF scene was processed automatically and interfered with categorization of the HSF scene. fMRI results revealed that this semantic interference effect was associated with increased activation in the inferior frontal gyrus, the superior parietal lobules, and the fusiform and parahippocampal gyri. Furthermore, a connectivity analysis (psychophysiological interaction) revealed that the semantic interference effect resulted in increasing connectivity between the right fusiform and the right inferior frontal gyri. Results support influential models suggesting that, during scene categorization, LSF information is processed rapidly in the pFC and activates plausible interpretations of the scene category. These coarse predictions would then initiate top–down influences on recognition-related areas of the inferotemporal cortex, and these could interfere with the categorization of HSF information in case of semantic dissimilarity to LSF.