Huntington’s disease (HD) is a severe genetic neurodegenerative disorder. Cortex, striatum, and their connectivity are mostly affected by this pathology. Numerous studies have delved into the dysfunction of striatal spiny projection neurons (SPNs) in HD; however, several questions still remain unanswered: are certain populations of striatal neurons spared by HD? Does the extent of impairment vary among the different cell types? What is the timing of onset for functional alterations? To answer these outstanding inquiries, we performed whole-cell patch clamp recordings on mouse brain slices of wild-type and R6/2 mice – a transgenic mouse model of HD – by analyzing the electrophysiological changes within SPNs and the three major populations of striatal interneurons – fast-spiking (FS-INs), low-threshold spiking (LTS-INs) and cholinergic (Ch-INs) – at two different disease stages. In the early stages of HD, alterations in action potential shape were observed in SPNs and FS-Ins. However, a significant reduction of spontaneous excitatory post-synaptic currents frequency occurred only in FS-INs and not in SPNs. Conversely, as HD progressed to its late stages, both MSNs and FS-INs displayed significant functional impairments. The analysis of LTS-INs and Ch-INs did not show alterations suggesting their preservation from HD-related damage. Collectively, our findings underscore the existence of a different vulnerability of striatal neurons to HD and indicate a specific temporal onset for cell impairments. Furthermore, they highlight the pivotal role of FS-INs in giving rise to changes in the complexity of striatal circuit dynamics in HD, as these interneurons appeared to be the earliest affected by the pathology.