Currently, the best method to well control the spread of COVID-19 without severe mental health problems is to reach herd immunity. Therefore, the vaccination rate of the COVID-19 vaccine is critical. Among the populations, children are the vulnerable ones to get vaccinated; therefore, it is important to assess parents’ and guardians’ willingness to have their children vaccinated. The present systematic review and meta-analysis synthesized evidence to estimate the parents’ acceptance rate of COVID-19 vaccination toward their children. Additionally, factors explaining the acceptance rate were investigated. Four academic databases (PubMed, Scopus, Web of Science, and ProQuest) together with Google Scholar were searched, and the references of the included publications were searched as well. Using the PECO-S framework (population, exposure, comparison, outcome, and study design), observational studies of cross-sectional, cohort, or case-control studies were included. The outcome was parents’ or guardians’ willingness to let their children be vaccinated. The studies included in the present review were restricted to English and peer-reviewed papers published between December 2019 and July 2022. A total of 98 papers across 69 different countries with 413,590 participants were included. The mean age of the parents was 39.10 (range: 18–70) years and that of their children was 8.45 (range: 0–18) years. The pooled estimated prevalence of parental acceptance to vaccinate their children with the COVID-19 vaccine was 57% (98 studies, 95% CI: 52–62%, I2: 99.92%, τ2: 0.06). Moreover, data collection time was a significant factor explaining parental willingness in the multivariable meta-regression, with a 13% decrease in parental willingness by each month increase in time, explaining 11.44% of variance. Qualitative synthesis results showed that parents’ COVID-19 vaccine knowledge, trust in theCOVID-19 vaccine, and facilitators in vaccination (e.g., low cost, good vaccine accessibility, and government incentive) were significant factors for higher willingness, while mental health problems (e.g., having worries and psychological distress) were significant factors for lower willingness. Given that the acceptance rate was relatively low (57%) and does not achieve the requirement of herd immunity (i.e., 70%), governments and healthcare authorities should try to elevate parents’ knowledge and trust in the COVID-19 vaccine, facilitate in vaccination, and reduce their mental difficulties to improve the overall vaccination rate among children.