Objectives <p>This systematic review aimed to assess the impact of early loss of primary teeth on children’s Oral Health-Related Quality of Life (OHRQoL).</p> Materials and methods <p>Electronic searches were conducted in eight databases, including grey literature, up to February 2025. The PECOS strategy was employed to identify studies evaluating the impact of early loss of primary teeth on children’s OHRQoL. Studies evaluating permanent tooth loss were excluded. The risk of bias in the included studies was evaluated using Joanna Briggs’ checklists for observational studies and the Cochrane RoB 2 tool for randomized clinical trials. A random-effect meta-analysis was conducted comparing the mean scores of OHRQoL questionnaires between children with and without early loss of primary teeth. The certainty of evidence was assessed using the GRADE approach.</p> Results <p>Five studies were included in the systematic review and three in the meta-analysis. Three studies fulfilled all items of the risk of bias checklists. The meta-analysis revealed that children with early loss of primary molars scored an average of 14.38 points higher on the OHRQoL questionnaire (95% CI: 2.13–26.64) compared to those without early primary molar loss, indicating a poorer OHRQoL. The certainty of evidence was considered very low.</p> Conclusions <p>The early loss of primary molars negatively impacted the OHRQoL of schoolchildren aged 8 to 10 years, as evidenced by higher OHRQoL scores.</p> Clinical relevance <p>The findings directly affect clinical practice, indicating that early loss of primary molars is associated with poorer OHRQoL in children aged 8 to 10 years. This information is valuable for dentists, pediatricians, and other healthcare professionals involved in children’s oral health care.</p> Registration <p>This systematic review was registered under the protocol registration code CRD42023439971.</p>