The treatment of infants with trisomy 21 (TS21) with a myostimulation plate can improve their development and quality of life. The manufacture of these plates requires an accurate cast of the maxilla, and their efficacy relies on their stability and retention. As such, the quality of the impression is a determining factor. The lack of commercially available stock trays for infants with TS21 creates difficulties, including inadequate impression quality and the risk of inhaling impression material. The present technique simplifies impression making for infants with TS21 from 3 months of age to when their maxillary deciduous teeth erupt by using computer-aided design and computer-aided manufacturing (CAD-CAM) impression trays. Sixty-five stored gypsum maxillary casts from infants with TS21 that had been used to manufacture myostimulation plates were analyzed to select four differently sized representative casts for designing the impression trays. A CAD software program was used to digitally shape four sizes of the impression tray from the selected gypsum casts. Practitioners interested in this approach can download and export the standard tessellation language (STL) files using a quick response (QR) code. The impression trays should be manufactured with the stereolithography additive technique using biocompatible resin. This technique allows practitioners to make accurate maxilla impressions for infants with TS21 by manufacturing their own impression trays using the free-access STL files rather than the cumbersome conventional method.