This study aims at exploring disability, health-related quality of life (HrQoL), psychological distress, and psychological features in post-stroke patients with chronic pain. An observational cross-sectional study involving 50 post-stroke patients (25 with chronic pain and 25 without pain) was conducted. The primary outcome was the self-reported level of disability and HrQoL which were both assessed through the Stroke Impact Scale 3.0. Both psychological distress and specific psychological features (i.e., self-efficacy, coping strategies, psychological flexibility, perceived social support) were examined. Post-stroke patients with chronic pain reported statistically significant higher levels of disability and worse HrQoL, higher psychological distress and inflexibility, as well as a lower level of self-efficacy and problem-oriented coping strategies than patients without pain (p < 0.001). Finally, correlation analysis in the group of stroke survivors with pain showed that higher levels of disability were significantly related to higher psychological distress. This study confirms the negative influence of chronic pain on disability and HrQoL in post-stroke patients and presents preliminary insights on the association between chronic pain, disability, HrQoL, psychosocial distress, and the patient’s approach in dealing with personal difficulties and emotions. These findings carry further implications for multidisciplinary management of post-stroke patients with chronic pain.