BACKGROUND: Muscle strength is important for young people with Down syndrome as they make the transition to adulthood, because their workplace activities typically emphasise physical rather than cognitive skills. Muscle strength is reduced up to 50% in people with Down syndrome compared to their peers without disability. Progressive resistance training improves muscle strength and endurance in people with Down syndrome. However, there is no evidence on whether it has an effect on work task performance or physical activity levels. The aim of this study is to investigate if a student-led community-based progressive resistance training programme can improve these outcomes in adolescents and young adults with Down syndrome. METHODS: A randomised controlled trial will compare progressive resistance training with a control group undertaking a social programme. Seventy adolescents and young adults with Down syndrome aged 14-22 years and mild to moderate intellectual disability will be randomly allocated to the intervention or control group using a concealed method. The intervention group will complete a 10-week, twice a week, student-led progressive resistance training programme at a local community gymnasium. The student mentors will be undergraduate physiotherapy students. The control group will complete an arts/social programme with a student mentor once a week for 90 minutes also for 10 weeks to control for the social aspect of the intervention. Work task performance (box stacking, pail carry), muscle strength (1 repetition maximum for chest and leg press) and physical activity (frequency, duration, intensity over 7-days) will be assessed at baseline (Week 0), following the intervention (Week 11), and at 3 months post intervention (Week 24) by an assessor blind to group allocation. Data will be analysed using ANCOVA with baseline measures as covariates. DISCUSSION: This paper outlines the study protocol for a randomised controlled trial on the effects of progressive resistance training on work task performance and physical activity for adolescents and young adults with Down syndrome. The intervention addresses the impairment of muscle weakness which may improve work task performance and help to increase physical activity levels. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12609000938202.