Background Most stroke survivors have sustained upper limb impairment in their distal joints. An electromyography (EMG)-driven wrist/hand exoneuromusculoskeleton (WH-ENMS) was developed previously. The present study investigated the feasibility of a home-based self-help telerehabilitation program assisted by the aforementioned EMG-driven WH-ENMS and its rehabilitation effects after stroke. Methods Persons with chronic stroke (n = 11) were recruited in a single-group trial. The training progress, including the training frequency and duration, was telemonitored. The clinical outcomes were evaluated using the Fugl–Meyer Assessment (FMA), Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), Motor Functional Independence Measure (FIM), and Modified Ashworth Scale (MAS). Improvement in muscle coordination was investigated in terms of the EMG activation level and the Co-contraction Index (CI) of the target muscles, including the abductor pollicis brevis (APB), flexor carpi radialis-flexor digitorum (FCR-FD), extensor carpi ulnaris-extensor digitorum (ECU-ED), biceps brachii (BIC), and triceps brachii (TRI). The movement smoothness and compensatory trunk movement were evaluated in terms of the following two kinematic parameters: number of movement units (NMUs) and maximal trunk displacement (MTD). The above evaluations were conducted before and after the training. Results All of the participants completed the home-based program with an intensity of 63.0 ± 1.90 (mean ± SD) min/session and 3.73 ± 0.75 (mean ± SD) sessions/week. After the training, motor improvements in the entire upper limb were found, as indicated by the significant improvements (P < 0.05) in the FMA, ARAT, WMFT, and MAS; significant decreases (P < 0.05) in the EMG activation levels of the APB and FCR-FD; significant decreases (P < 0.05) in the CI of the ECU–ED/FCR–FD, ECU–ED/BIC, FCR–FD/APB, FCR–FD/BIC, FCR–FD/TRI, APB/BIC and BIC/TRI muscle pairs; and significant reductions (P < 0.05) in the NMUs and MTD. Conclusions The results suggested that the home-based self-help telerehabilitation program assisted by EMG-driven WH-ENMS is feasible and effective for improving the motor function of the paretic upper limb after stroke. Trial registration ClinicalTrials.gov. NCT03752775; Date of registration: November 20, 2018.