Upper extremity (UE) weakness and/or paralysis following spinal cord injury (SCI) can lead to a limited capacity to perform activities of daily living (ADL). Such disability significantly reduces an individual’s level of independence. Further, restoration of UE motor function in people with SCI remains a high priority in rehabilitation and the field of assistive technology. The overall goal of this study was to evaluate the effects of a myoelectric-powered wearable orthosis (MPWO) manufactured by MyoMo, Inc. (Boston, MA) for UE movement assistance on ameliorating UE motor function in order to improve ADL and quality of life in people with SCI. Two male participants with chronic incomplete SCI (iSCI), a 75- and a 31-year-old with AIS D and B, respectively, underwent 18 sessions (over 6 weeks) of UE movement rehabilitation using the MPWO. Handgrip strength, active range of motion (AROM) of the hand, response time to initiate a movement, and muscles activations were examined before and after the rehabilitation training using the MPWO. The response time to initiate UE movements decreased, and handgrip strength and AROM improved after training with the MPWO. These preliminary data suggest that rehabilitation with the use of the UE-MPWO device could enhance the participants’ UE activities that led to improved function.Clinical Relevance— These preliminary results from two individuals with iSCI suggest that training with UE-MPWO assistive devices may improve UE utilization during ADL for individuals with muscle weakness or paralysis but still possessing residual voluntary muscle activation capabilities.