Venezuelan and western equine encephalitis viruses (VEEV and WEEV; Alphavirus; Togaviridae) are mosquito-borne pathogens causing central nervous system disease in humans, equids, and mouse infection models. The route(s) of alphavirus entry into the CNS following peripheral infection is not well understood. Furthermore, gaps in knowledge remain regarding the specific areas of the brain affected by the disease. In this study, we injected VEEV or WEEV, engineered to express bioluminescent or fluorescent reporters (fLUC and DsRed, respectively), into the footpads of outbred CD-1 mice to simulate transmission by a mosquito. Reporter expression serves as markers of virus replication, allowing us to track the progress of infection. In vivo and ex vivo imaging were used to identify early entry sites of these alphaviruses in the CNS. We observed that the circumventricular organs, areas of the brain where the blood-brain barrier is naturally absent, consistently showed the earliest signs of infection with VEEV and WEEV. Infection progressed into the brain and was observed to following a pattern of spread similar to the progression of neurodegenerative ‘prion-like’ diseases such as Parkinson’s disease. Stereological assessment revealed that dopaminergic neurons of the substantia nigra are exquisitely sensitive to virus-induced degeneration and support robust levels of virus replication. Taken together, these findings provide evidence for a previously unknown route of virus entry into the CNS, and help to explain neurological sequelae (post-encephalitic parkinsonism) observed among human survivors of alphavirus encephalitides.