Objective To investigate prevalence, incidence and profile of musculoskeletal injuries in para athletes. Design Systematic review. Data sources Searches were conducted in MEDLINE, EMBASE, AMED, SPORTSDiscus, CINAHL and hand searching. Eligibility criteria Studies were considered if they reported prevalence or incidence of musculoskeletal injuries in para athletes. Study selection, data extraction and analysis followed the protocol. Meta-analyses were conducted to estimate the prevalence and incidence rate among studies and subgroup analyses investigated whether methodological quality and sample size of the studies influenced on the estimated injury prevalence and incidence. The Grading of Recommendations Assessment, Development and Evaluation system determined the strength of evidence. Results Forty-two studies were included. The prevalence of musculoskeletal injuries was 40.8% (95% CI 32.5% to 49.8%). Because of imprecision, indirectness and inconsistency, the strength of evidence was very low quality. The incidence of musculoskeletal injuries was 14.3 injuries per 1000 athlete-days (95% CI 11.9 to 16.8). The strength of evidence was low quality because of imprecision and indirectness. The subgroup analyses revealed that the sample size influenced on estimated injury prevalence and methodological quality influenced on estimated incidence. Injuries were more prevalent in the shoulder, for non-ambulant para athletes, and in the lower limbs, for ambulant para athletes. Summary/conclusion Para athletes show high prevalence and incidence of musculoskeletal injuries. Current very low-quality and low-quality evidence suggests that future high-quality studies with systematic data collection, larger sample size and specificities of para athletes are likely to change estimates of injury prevalence and incidence in para athletes. PROSPERO registration number CRD42020147982.