Digital technology has been introduced in prosthodontics, and it has been widely used in denture duplication instead of a conventional denture duplication technique. However, research comparing different denture duplication techniques and how they affect the fitting accuracy of the denture base is scarce. The aim was to assess the impact of duplication techniques on the accuracy of the fitting surface of computer-aided design and manufacturing (CAD-CAM) milled, 3D-printed, and injection-molded complete denture bases (CDBs). This study involved fabricating a mandibular complete denture base with three marked dimples as reference marks (A, B, and C at the incisive papilla, right molar, and left molar areas) using a conventional compression molded technique. This denture was then scanned to generate a standard tessellation language (STL) file; after that, it was duplicated using three different techniques (milling, 3D printing, and injection molding) and five denture base resin materials-two milled CAD-CAM materials (AvaDent and IvoBase), two 3D-printed materials (NextDent and HARZ Labs), and one injection-molded material (iFlextm). Based on the denture base type, the study divided them into five groups (each with n = 10). An evaluation of duplication accuracy was conducted on the fitting surface of each complete denture base (CDB) using two assessment methods. The first method was a two-dimensional evaluation, which entailed linear measurements of the distances (A-B, A-C, and B-C) between reference points on both the scanned reference mandibular denture and the duplicated dentures. Additionally, a three-dimensional superimposition technique was employed, involving the overlay of the STL files of the dentures onto the reference denture's STL file. The collected data underwent statistical analysis using a one-way analysis of variance and Tukey's pairwise post hoc tests. Both evaluation techniques showed significant differences in fitting surface accuracy between the tested CDBs (p ˂ 0.001), as indicated by one-way ANOVA. In addition, the milled CDBs (AvaDent and IvoBase) had significantly higher fitting surface accuracy than the other groups (p ˂ 0.001) and were followed by 3D-printed CDBs (NextDent and HARZ Labs), while the injection-molded (iFlextm) CDBs had the lowest accuracy (p ˂ 0.001). The duplication technique of complete dentures using a CAD-CAM milling system produced superior fitting surface accuracy compared to the 3D-printing and injection-molded techniques.