We investigated the combination of robot-assisted rehabilitation (RT) using a single-joint hybrid assistive limb (HAL-SJ) and botulinum toxin A (BTX-A) as therapy for paretic arm with spasticity in post-stroke patients. Participants were seven patients (4 females, 3 males; mean (±SD) age: 60.6 ± 8.4 years) who had spastic hemiplegia following chronic stroke. On the day following BTX-A injection, we started RT, which was performed for 20 sessions of 60 min each over a two-week period. Clinical outcome measures, including Fugl-Meyer Assessment (FMA), Motor Activity Log (MAL), and Disability Assessment Scale (DAS), and cortical activity were evaluated at baseline, and two weeks, and four months following BTX-A injection. Cortical activity associated with elbow joint movement of the affected arm was assessed via functional near infrared spectroscopy (fNIRS). FMA, MAL, and DAS scores significantly improved at two weeks and four months (p < 0.05), except DAS scores at four months (p = 0.068). The fNIRS study showed that cortical activation increased in the ipsilesional primary sensorimotor area at two weeks and at the four months follow-up. Our pilot study showed that the combination of RT and BTX-A therapy was an effective approach for treating spastic hemiplegia due to stroke, and functional imaging study showed neuroplasticity induced by the treatment.