Dysphagia is a frequent and burdensome symptom in patients with all forms of neuronal ceroid lipofuscinosis (NCLs), yet its underlying mechanisms remain largely unclear. Although the NCLs are primarily classified as neurodegenerative diseases of the central nervous system (CNS), growing evidence suggests that structures outside the brain—potentially including those involved in the coordination of swallowing—also contribute to disease pathology. These structures include the tongue, esophagus, masseter muscle, in addition to critical brainstem cranial nerve nuclei. In this study, we explored the pathophysiological basis of dysphagia using three well-established NCL mouse models: CLN1 (Ppt1⁻/⁻), CLN2 (Tpp1R207X/R207X), and CLN3 (Cln3Δex7/8). Across all models, we observed consistent structural abnormalities within the oropharyngeal and esophageal regions, including degeneration of the tongue, masseter, and esophageal muscles, along with a reduction in the number of enteric neurons in the esophagus. We also identified pathological changes in key brainstem cranial nerve nuclei known to regulate swallowing, by innervating the muscles involved in swallowing or receiving sensory feedback from them. To assess therapeutic potential, we applied systemic AAV-mediated gene therapy early in life. This treatment partially prevented neuromuscular and esophageal degeneration and neuroinflammatory changes within the brainstem. Together, these findings reveal that dysphagia in NCL likely arises from both central and peripheral pathologies. Our data emphasize the need for therapeutic strategies that target not only the CNS but also peripheral tissues, with the goal of improving feeding and swallowing function in patients with NCL.