Purpose: The purpose of this study was to compare the changes in oral health-related quality of life (OHRQoL) scores in children treated for Early Childhood Caries (ECC) under general (GA) and local anesthesia (LA). Methods: A quasi-experimental study was carried out on 73 children, with 37 in the GA group and 36 in the LA group. The early childhood oral health impact scale (ECOHIS) was used to measure OHRQoL, with the type of anesthesia (LA or GA) serving as the explanatory variable. A Friedman test was used to assess the difference between the LA and GA groups at baseline, one-week, and one-month follow-up points. Results: The results showed a significant difference in the overall mean ECOHIS scores between the LA and GA groups at 1-week (LAmean ± SD = 6.12 ± 1.11, GAmean ± SD = 5.50 ± 0.88; P = 0.01) and 1-month (LAmean ± SD = 5.87 ± 1.12, GAmean ± SD = 4.96 ± 0.99; P < 0.001) follow-up points. Irrespective of the administered anesthesia, a significant (P < 0.001) reduction in the mean score for dental pain was observed at both 1-week (mean ± SD = 1.30 ± 1.16) and 1-month (mean ± SD = 0.81 ± 0.89) timepoints after the treatment, as compared to the baseline assessment (mean ± SD = 2.02 ± 1.02). Conclusion: Early treatment for ECC reduces pain, restore normal activities, and improves the quality of life of affected children. Specifically, GA was found to be more beneficial for both children and parents. However, further studies using more robust study designs and carefully considering related factors are necessary to confirm these findings.