A limited amount of systematic literature reviews on the association between malocclusions and oral health-related quality of life (OHRQOL) summarize inconclusive results. Therefore, we conduct a systematic review and meta-analysis on the association of malocclusions with OHRQOL in children. Relevant studies were identified in Pubmed, Embase, Cochrane, Google Scholar and other databases. All studies with data on malocclusions or orthodontic treatment need and OHRQOL in children were included. Methodological quality of the studies was assessed with the Newcastle-Ottawa Scale (NOS). Random effects models were used to estimate summary effect measures for the association between malocclusion and OHRQOL in a continuous and a categorical data analysis. Tests for heterogeneity, publication bias and sensitivity of results were performed. In total, 40 cross-sectional studies were included in the meta-analyses. Summary measures of the continuous data show that OHRQOL was significantly lowered in children with malocclusions (standardized mean difference (95 % CI] = 0.29 (0.19-0.38)). The summary odds ratio for having an impact on OHRQOL was 1.74 times higher in children with malocclusion than in children without malocclusions. Heterogeneity among studies was partly explained by malocclusion assessment, age of the children and country of study conduction. Our results provide evidence for a clear inverse association of malocclusion with OHRQOL. We also showed that the strength of the association differed depending on the age of the children and their cultural environment. Dentists benefit from understanding the patient differences regarding the impact of malocclusions.