Abstract  Huntington's disease (HD) is a heritable neurodegenerative disorder, with heart disease implicated as one major cause of death. While the responsible mechanism remains unknown, autonomic nervous system (ANS) dysfunction may play a role. We studied the cardiac phenotype in R6/1 transgenic mice at early (3 months old) and advanced (7 months old) stages of HD. While exhibiting a modest reduction in cardiomyocyte diameter, R6/1 mice had preserved baseline cardiac function. Conscious ECG telemetry revealed the absence of 24‐h variation of heart rate (HR), and higher HR levels than wild‐type littermates in young but not older R6/1 mice. Older R6/1 mice had increased plasma level of noradrenaline (NA), which was associated with reduced cardiac NA content. R6/1 mice also had unstable R–R intervals that were reversed following atropine treatment, suggesting parasympathetic nervous activation, and developed brady‐ and tachyarrhythmias, including paroxysmal atrial fibrillation and sudden death. c‐Fos immunohistochemistry revealed greater numbers of active neurons in ANS‐regulatory regions of R6/1 brains. Collectively, R6/1 mice exhibit profound ANS‐cardiac dysfunction involving both sympathetic and parasympathetic limbs, that may be related to altered central autonomic pathways and lead to cardiac arrhythmias and sudden death.