In this study, a systematic investigation was performed to estimate the prevalence of head lice infestation, and to determine the factors affecting the prevalence of heterogeneity among primary school-aged children in Iran. A comprehensive search was fulfilled in international databases, including MEDLINE, Scopus, Web of Science, and Embase, to identify the articles on the prevalence of pediculosis. So, all the cross-sectional epidemiological studies evaluating the prevalence of pediculosis were covered without any restrictions. A random-effects model was used to assess the pooled prevalence. A meta-regression method was applied to determine the factors affecting the heterogeneity among the studied population. An analysis was performed on 67 studies with a total sample size of 358,053. The total pooled estimate for the prevalence of pediculosis in boys and girls was 7.52% (95% CI: 6.15–9.03), 1.99% (95% CI: 1.25–2.89), and 8.97% (95% CI: 721–10.91), respectively. The highest and lowest pooled prevalence was in Hormozgan (southern Iran) (29.21%; 95% CI: 8.89–55.34) and Isfahan (Central Iran) (0.69%; 95% CI: 0.59–0.80), respectively. Based on the results of the univariate meta-regression, gender and father's job showed a significant direct association with the prevalence of pediculosis, but the sample size had significant inverse relations with the prevalence of pediculosis. This study demonstrated that pediculosis is a common public health problem affecting school-aged children with a relatively high prevalence in Iran, especially among girls.