Purpose The aim of this study was to screen for keratoconus (KC) in a sample of children with Down syndrome (DS) and to correlate the changes of combined Scheimpflug and optical coherence tomography imaging in these children and to compare it with an age-matched control group with healthy cornea. Patients and methods This was a prospective, case–control, analytic study that included 52 eyes of 26 children, who were divided into two groups: 13 with DS (group A) and 13 age-matched healthy controls (group B). Both groups were evaluated using anterior segment optical coherence tomography (AS-OCT) and Scheimpflug camera topographer (Sirius, CSO). Results KC-like features were detected in 61.5% of the patients in the DS group. Assessment of the corneal parameters showed statistically significant correlation between Sirius topography and AS-OCT epithelium and pachymetry maps parameters in the DS group. Conclusion Corneal features compatible with the diagnosis of KC were common findings in children with DS. Combined use of AS-OCT epithelial mapping and corneal topography is of high significance and can be used for screening and early detection of KC in patients with DS.