Humans and animals use information obtained from the local visual scene to orient themselves in the wider world. Although neural systems involved in scene perception have been identified, the extent to which processing in these systems is affected by previous experience is unclear. We addressed this issue by scanning subjects with functional magnetic resonance imaging (fMRI) while they viewed photographs of familiar and unfamiliar locations. Scene-selective regions in parahippocampal cortex (the parahippocampal place area, or PPA), retrosplenial cortex (RSC), and the transverse occipital sulcus (TOS) responded more strongly to images of familiar locations than to images of unfamiliar locations, with the strongest effects (>50% increase) in RSC. Examination of fMRI repetition suppression (RS) effects indicated that images of familiar and unfamiliar locations were processed with the same degree of viewpoint-specificity; however, increased viewpoint-invariance was observed as individual scenes became more familiar over the course of a scan session. Surprisingly, these within-scan-session viewpoint-invariant RS effects were only observed when scenes were repeated across different trials but not when scenes were repeated within a trial, suggesting that within-trial and between-trial RS effects may index different aspects of visual scene processing. The sensitivity to environmental familiarity observed in the PPA, RSC and TOS supports earlier claims that these regions mediate the extraction of navigationally-relevant spatial information from visual scenes. As locations become familiar, the neural representations of these locations become enriched, but the viewpoint invariance of these representations does not change.