Persistent breathlessness >28 days after acute COVID-19 infection has been identified as a highly debilitating post-COVID symptom. However, the prevalence, risk factors, mechanisms and treatments for post-COVID breathlessness remain poorly understood. We systematically searched PubMed and Embase for relevant studies published from 1 January 2020 to 1 November 2021 (PROSPERO registration number: CRD42021285733) and included 119 eligible papers. Random-effects meta-analysis of 42 872 patients with COVID-19 reported in 102 papers found an overall prevalence of post-COVID breathlessness of 26% (95% CI 23-29) when measuring the presence/absence of the symptom, and 41% (95% CI 34-48) when using Medical Research Council (MRC)/modified MRC dyspnoea scale. The pooled prevalence decreased significantly from 1-6 months to 7-12 months post-infection. Post-COVID breathlessness was more common in those with severe/critical acute infection, those who were hospitalised and females, and was less likely to be reported by patients in Asia than those in Europe or North America. Multiple pathophysiological mechanisms have been proposed (including deconditioning, restrictive/obstructive airflow limitation, systemic inflammation, impaired mental health), but the body of evidence remains inconclusive. Seven cohort studies and one randomised controlled trial suggested rehabilitation exercises may reduce post-COVID breathlessness. There is an urgent need for mechanistic research and development of interventions for the prevention and treatment of post-COVID breathlessness.