Neurovascular abnormalities occur in many brain disorders and neurodegenerative diseases, including Huntington’s disease (HD). We demonstrate that the brain vessel density is higher in mice and patients with HD than in controls. A fraction of these cortical blood vessels in the brains of HD mice is nonreactive to carbogen. Such impaired blood vessels in HD brains is caused by an increased ability of HD astrocytes to produce more VEGF and inflammatory mediators. The resultant impaired VR may hinder cerebral hemodynamics and increase brain atrophy during HD progression. Our study presents the first evidence of impairment of VR in HD. The MRI and mechanistic findings from our experiments have established a foundation for using VR as a prognostic HD marker. This study has been selected by HD Insights <http://www.hdinsights.org> as one of the most influential papers in HD of the past year.