Extraction of the permanent first molars is sometimes necessitated in children and adolescents due to deep carious lesions or developmental defects. To estimate the prevalence of spontaneous space closure after extraction of permanent first molars and identify factors associated with it. Unrestricted searches in five databases for human studies until February 2024. Longitudinal before-and-after (cohort) human studies assessing eruption of the permanent second molars and spontaneous space closure after extraction of the permanent first molar. Study selection, data extraction, and risk of bias assessment were performed in duplicate. Random-effects meta-analyses of average spontaneous space closure prevalences and odds ratios (OR) with their 95% confidence intervals (CI) were performed, followed by meta-regression/sensitivity/reporting biases' analyses and evaluation of our confidence in effect estimates. Sixteen reports pertaining to 15 studies (1 prospective /14 retrospective) were included covering 1159 patients (ages 5.5-15.0 years [mean 10.0 years]; 45% male on average) and 2310 permanent second molars. The prevalence of spontaneous space closure was higher in the maxilla (nine studies; 85.3%; 95% CI = 73.7%-92.3%) than the mandible (11 studies; 48.1%; 95% CI = 34.5%-62.0%) to a significant extent (nine studies; OR = 7.77; 95% CI = 4.99-12.11; P < 0.001). For both maxillary/mandibular second molars, Demirjian category E was associated with increased space closure odds than earlier/later stages (P < 0.05). Spontaneous space closure in the mandible was seen more often for patients ages 8-10 years (compared with older patients; three studies; OR = 3.32; 95% CI = 1.73-6.36; P < 0.001) and when the mandibular permanent third molar was present (four studies; OR = 2.28; 95% CI = 1.67-3.09; P = 0.003). Additional analyses failed to find any significant modifying factors. The quality of evidence was very low in all instances due to the inclusion of retrospective studies with methodological issues. Existing evidence indicates that spontaneous space closure in children and adolescents after extraction of the permanent first molar is seen more often in the maxilla than the mandible. Extraction of the permanent first molar at the Demirjian stage E of the second molar and presence of the lower permanent third molar is associated with increased odds of space closure, but uncertainty persists, due to methodological issues of existing studies. PROSPERO (CRD42023395371).