Background This study investigates the impact of malocclusion on the oral health-related quality of life (OHRQoL) of 11-14-year-old children.Methods This cross-sectional study was conducted among 250 caregiver/child (11-14-year-olds) dyads seeking orthodontic consultation at the orthodontic center at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Oral health related quality of life (OHRQoL) was assessed using child perception questionnaire 11-14 (CPQ 11–14 ) and the Dental Aesthetic Index (DAI) was used to assess severity of malocclusion. CPQ 11–14 scores ranged from 0 to 64, with lower scores representing a better quality of life. Multivariate analysis of variance (MANOVA) was used to assess differences between domain and total CPQ 11–14 scores with the co-variates. Results The mean CPQ 11–14 score was 19.89±9.8. Mean scores for the global rating, oral symptoms, functional limitations, emotional well-being, and social well-being domains were 4.91±2.15, 5.26±3.22, 3.67±3.58, 3.98±3.89 and 2.08±2.98, respectively. The distribution of subjects across the four severity categories was minor/none – 37%, definite – 22%, severe – 15% and very severe 24%. The overall and domain-specific scores of CPQ 11–14 varied across the different categories of malocclusion. In the comparisons by pairs, it was found that children with very severe malocclusion had significantly higher scores for the social well-being domain and global rating of oral health as compared to children with no/minor malocclusion (p<0.05). Conclusion Substantial variability in the well-being domain of CPQ 11–14 was observed among children with no/minor malocclusions as compared to children with severe malocclusions.