The aim of this study was to evaluate the craniofacial cephalometric characteristics of individuals with Down syndrome (DS), comparing them with healthy subjects. An electronic search was made in Pubmed, Embase, Lilacs, Scopus, Medline and Web of Science without imposing limitations on publication date or language. Studies were selecting following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The PECO acronym was applied as follows: P (population), individuals with DS; E, (exposition) diagnosis of DS; C (comparison), individuals without DS; O (outcomes) craniofacial characteristics based on cephalometric measurements. Independent reviewers performed data extraction and assessed the methodological quality of the articles using the Newcastle–Ottawa Quality-Assessment-scale. Seven case–control studies were included in meta-analysis. Given the variability of the cephalometric measurements used, only those that had been reported in at least three or more works could be included. Anterior cranial base length (SN), posterior cranial base length (SBa), total cranial base length (BaN), effective length of the maxilla (CoA), sagittal relationship between subspinale and supramentale (ANB), anterior facial height (NMe), and posterior facial height (SGo) values were significantly lower in the DS population than among control subjects. No significant differences were found in sagittal position of subspinale relative to cranial base (SNA) and sagittal position of supramentale relative to cranial base (SNB). Summarizing, individuals with DS present a shorter and flatter cranial base than the general population, an upper jaw of reduced sagittal dimension, as well as a tendency toward prognatic profile, with the medium third of the face flattened and a reduced anterior and posterior facial heights.