Background: This article presents the system architecture and validation of the NeuroSuitUp body–machine interface (BMI). The platform consists of wearable robotics jacket and gloves in combination with a serious game application for self-paced neurorehabilitation in spinal cord injury and chronic stroke. Methods: The wearable robotics implement a sensor layer, to approximate kinematic chain segment orientation, and an actuation layer. Sensors consist of commercial magnetic, angular rate and gravity (MARG), surface electromyography (sEMG), and flex sensors, while actuation is achieved through electrical muscle stimulation (EMS) and pneumatic actuators. On-board electronics connect to a Robot Operating System environment-based parser/controller and to a Unity-based live avatar representation game. BMI subsystems validation was performed using exercises through a Stereoscopic camera Computer Vision approach for the jacket and through multiple grip activities for the glove. Ten healthy subjects participated in system validation trials, performing three arm and three hand exercises (each 10 motor task trials) and completing user experience questionnaires. Results: Acceptable correlation was observed in 23/30 arm exercises performed with the jacket. No significant differences in glove sensor data during actuation state were observed. No difficulty to use, discomfort, or negative robotics perception were reported. Conclusions: Subsequent design improvements will implement additional absolute orientation sensors, MARG/EMG based biofeedback to the game, improved immersion through Augmented Reality and improvements towards system robustness.