BACKGROUND: Mouth breathing is closely related to the facial skeletal development and malocclusion. The purpose of this systematic review and meta-analysis was to assess the effect of mouth breathing on facial skeletal development and malocclusion in children. METHODS: An electronic search in PubMed, the Cochrane Library, Medline, Web of Science, EMBASE and Sigle through February 23rd, 2020, was conducted. Methodological quality assessments of the selected articles were performed using the Newcastle-Ottawa Scale. Review Manager 5.3, was used to synthesize various parameters associated with the impact of mouth breathing on facial skeletal development and malocclusion. RESULTS: Following full-text evaluations for eligibility, 7 studies (387 mouth-breathing subjects and 433 nasal-breathing controls) were included in the final quantitative synthesis; they were all high-quality. The included indicators were SNA (p>0.050), ANS-PNS (p>0.050), 1.NB (p>0.050), MP-H (p>0.050), FMA (p>0.050), SNB (MD: -1.99, P <0.0001), ANB (MD: 0.95, P = 0.0005), SN-OP (MD: 3.20, P < 0.0001), SNGoGn (MD: 4.34, P < 0.0001), 1-NA (MD: 0.72, P = 0.004), 1. NA (MD: 1.98, P = 0.020), 1-NB (MD: 1.06, P < 0.0001), SPAS (MD: -5.23, P < 0.0001), PAS (MD: -2.11, P < 0.0001), and C3-H (MD: -1.34, P < 0.0001). CONCLUSIONS: The results showed that mouth breathing can cause underdevelopment of the mandible. The mandible rotated backward and downward, and the occlusal plane was steep. However, there was little effect on the maxilla. In addition, mouth breathing presented a tendency of lip inclination of the upper and lower anterior teeth. Airway stenosis was common in mouth-breathing children. TRIAL REGISTRATION: crd-register@york.ac.uk; registration number CRD42019129198 KEYWORDS: Mouth breathing; Facial skeletal development; Children; Systematic review, Meta-analysis.