High-flow nasal cannula (HFNC) is a novel oxygenation approach in the management of acute respiratory distress syndrome (ARDS). This systematic review was focused on evaluating current evidence concerning the efficacy of HFNC in ARDS and its comparison with standard treatment approaches. For this review, a systematic search was undertaken in PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Web of Science, Cochrane Library, and Google Scholar to identify relevant studies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. All those studies that investigated the impact of HFNC on ARDS patients and were published in the English language were included. The literature search from all databases provided 6157 potentially relevant articles from PubMed (n = 1105), CINAHL (n = 808), Web of Science (n = 811), Embase (n = 2503), Cochrane database (n = 930), and Google Scholar (n = 46). After the exclusion of studies that did not fulfill the criteria, 18 studies were shortlisted for the scope of this systematic review. Among the included studies, five focused on HFNC's impact on COVID-19-related ARDS, whereas 13 studies focused on HFNC's impact on ARDS patients. Most studies demonstrated the efficacy of HFNC in managing ARDS, with some studies showing comparable efficacy and higher safety compared to noninvasive ventilation (NIV). This systematic review highlights the potential benefits of HFNC in ARDS management. The findings show that HFNC is effective in reducing the respiratory distress symptoms, the incidence of invasive ventilation, and the adverse events associated with ARDS. These findings can help clinical decision-making processes and contribute to the evidence base for optimal ARDS management strategies.