Background Awake prone positioning (APP) has been considered as a feasible treatment for patients with acute hypoxemic respiratory failure in non-intubated coronavirus disease 2019 (COVID-19). However, the efficacy and safety of APP remain uncertain. This meta-analysis aims to assess the effect of APP on intubation rate and mortality in COVID-19 patients with acute respiratory failure. Methods Relevant studies published from January 1, 2020, to June 17, 2022, were systematically searched. The primary outcomes were the intubation rate and mortality; the secondary outcome was the incidence of adverse events. Results Of 5746 identified publications, 22 were eligible for inclusion in the meta-analysis (N = 5146 patients). In comparison to the non-APP group, APP could decrease the intubation rates (OR 0.64; 95% CI 0.48-0.83; P = .001), particularly in the subgroup of the daily median duration of APP > 8 h and in the subgroup of receiving high flow nasal cannula (HFNC) or non-invasive ventilation (NIV). Patients treated with APP were associated with lower mortality rates (OR 0.61; 95% CI 0.45-0.81; P = .0008), but no mortality benefit was found in the APP group in the subgroup of randomized controlled trials (RCTs). No significant difference was found in the incidence of adverse events between the groups (OR 1.13; 95% CI 0.75-1.71; P = .56). Conclusion Our results demonstrated that APP could be an effective strategy to avoid intubation without detrimental effects in non-intubated patients with COVID-19, especially for patients requiring HFNC or NIV, and the daily APP duration with the target of minimally eight hours was suggested. In the subgroup of RCTs, the pooled results did not demonstrate any benefit of APP on mortality. Given the limited number of RCTs, further high-quality RCTs are needed to confirm the results. INPLASY registration number INPLASY2021110037.