Head and neck cancers are a heterogeneous group of neoplasms, which together comprise the sixth most common cancer globally. Breath biopsies are a non-invasive clinical investigation that detect volatile organic compounds (VOCs) in exhaled breath. This systematic review examines current applications of breath biopsy for the diagnosis of head and neck squamous cell carcinoma (HNSCC), including data on efficacy and utility, and speculates on the future uses of this non-invasive detection method. Medline, PubMed, Web of Science, Cochrane and Scopus, as well as the grey literature were searched using a search strategy developed to identify relevant studies on the role of breath biopsy in the diagnosis of HNSCC. All included studies were subject to a thorough methodological quality assessment. The initial search generated a total of 1443 articles, 20 of which were eligible for review. A total of 660 HNSCC samples were investigated across the included studies. 3,7-dimethylundecane and benzaldehyde were among several VOCs to be significantly correlated with the presence of HNSCC compared to healthy controls. We show that current breath biopsy methods have high accuracy, specificity and sensitivity for identifying HNSCC. However, further studies are needed given the reported poor quality of the included studies.