Background: In this study, a novel electromechanical robotic exoskeleton was developed for the rehabilitation of distal joints. The objective was to explore the functional MRI and the neurophysiological changes in cortical-excitability in response to exoskeleton training for a 9-year chronic stroke patient. Case-Report: The study involved a 52-year old female patient with a 9-year chronic stroke of the right hemisphere, who underwent 20 therapy sessions of 45 min each. Cortical-excitability and clinical-scales: Fugl-Mayer (FM), Modified Ashworth Scale (MAS), Brunnstrom-Stage (BS), Barthel-Index (BI), Range of Motion (ROM), were assessed pre-and post-therapy to quantitatively assess the motor recovery. Clinical Rehabilitation Impact: Increase in FM wrist/hand by 6, BI by 10, and decrease in MAS by 1 were reported. Ipsilesional Motor Evoked Potential (MEP) (obtained using Transcranial Magnetic Stimulation) was increased by 98 μV with a decrease in RMT by 6% and contralesional MEP was increased by 43 μV with a decrease in RMT by 4%. Laterality Index of Sensorimotor Cortex (SMC) reduced in precentral- gyrus (from 0.152 to -0.707) and in postcentral-gyrus (from 0.203 to -0.632). Conclusion: The novel exoskeleton-based training showed improved motor outcomes, cortical excitability, and neuronal activation. The research encourages the further investigation of the potential of exoskeleton training.