Oropharyngeal dysphagia (OD) is a common post-stroke complication and is associated with respiratory infections. The aim was to assess the biomechanical impairments in swallow function and the afferent and efferent swallowing pathways impairing swallow safety in chronic post-stroke patients. We studied 30 patients with unilateral stroke and chronic OD (> 3 months from stroke onset) with impaired safety of swallow (Penetration-Aspiration Scale [PAS] ≥ 2). We evaluated the efficacy, safety, and kinematics of the swallow response (residue, PAS, laryngeal vestibule closure time [LVCT]) with videofluoroscopy, sensory evoked potentials to pharyngeal electrical stimulation (pSEP), and pharyngeal motor evoked potentials (pMEP) to transcranial magnetic stimulation of both hemispheres. Mean age of patients was 70.1 ± 10.9 years (7 women). Stroke severity at onset was moderate (NIHSS median 10 [IQ range 3-11.5]), and modified Rankin Scale 2.8 ± 1.3. Mean PAS was 5.1 ± 1.9; prevalence of delayed LVCT was 86.7% and 30% presented aspirations. Pharyngeal hypoesthesia was present in 46.7% of patients and 92.3% showed abnormally asymmetrical pSEPs when comparing the ipsilesional with the contralesional hemisphere. Increased duration of swallow was associated with lower pSEP amplitude (P1-N2) in the contralesional hemisphere (p = 0.033). Patients with right hemispheric strokes showed greater reduction of pSEPs amplitude (N1-P1, p = 0.049). In contrast, pharyngeal resting motor threshold and pMEPs were symmetric in 73.3% patients without the physiologic hemispheric dominance. Mild-to-moderate disabled chronic post-stroke patients with OD presented severe impaired biomechanics of swallow response and high prevalence of aspirations. Initial results from the neurophysiological evaluation demonstrated prevalent impairments with disrupted integration of pharyngeal sensory inputs and reduced cortical excitability of efferent pathways. Patients with right hemispheric strokes showed poorer neurophysiological responses.