© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. Introduction Rates of physical inactivity among people with physical disabilities are substantially higher than in the general population and access to home-based tailored exercise programmes is almost non-existent. Using a theory-driven eHealth platform, an innovative exercise programme referred to as movement-to-music (M2M) will be delivered as a customised, home-based exercise intervention for adults with mobility disabilities. Methods and analysis Participants are being recruited for this type 1 hybrid design based effectiveness trial through outpatient clinics at a large rehabilitation centre and randomised to one of three groups: (1) M2M, (2) M2M plus social networking (M2M plus) and (3) attention control (AC). The intervention includes a 12-week adoption phase, 12-week transition phase and 24-week maintenance phase, at which the collection of objective measures on exercise, fitness and self-reported measures on health will be obtained at the start of each phase and at follow-up. The study compares the effectiveness of M2M and M2M plus in increasing physical activity (primary outcome), adherence, fitness and physical functioning compared with the AC group and examines the mediators and moderators of the treatment effect. Ethics and dissemination The Institutional Review Board of The University of Alabama at Birmingham granted full approval: (IRB-160923002). Dissemination of findings will include publication in peer-reviewed journals, presentations at regional, national and/or international meetings, and the National Center on Health, Physical Activity and Disability (NCHPAD, www.nchpad.org). This study will strengthen our understanding of the potential benefits of eHealth exercise interventions for people with physical disabilities and build on strategies that aim to recruit larger samples in exercise trials. Trial registration number NCT03024320; Pre-results.