The aim of this study was to evaluate and compare the fracture resistance of a single-unit fixed prosthesis, using a CAD/CAM PMMA material and two printed materials (3DPPa and 3DPPb). A typodont with a specific preparation for a full crown was used; a digital impression was made with a state-of-the-art scanner (PrimeScan^TM, Dentsply-Sirona^TM, New York, NY, USA), and a full coverage restoration was designed using a biogeneric design proposal by means of specific software (InLAB 22.1, Dentsply-Sirona, NY, USA). Sixty crowns were prepared, divided into three groups according to the material: 3DPPa (n = 20), 3DPPb (n = 20), both 3D-printed from the .STL file with a resolution of 50 μm, and PMMA (n = 20) milled-derived, which were subjected to a thermocycling process. A universal testing machine (Universal/Tensile Testing Machine, Autograph AGS-X Series) with integrated software (TRAPEZIUM LITE X) equipped with a 20 kN load cell was used to determine the fracture resistance. Significant differences were found by Kruskal–Wallis test and multiple comparisons (p < 0.05) in fracture resistance between materials. The fracture resistance for the PMMA material was higher, and the standard deviation was lower (x = 1427.9; sd = 36.9 N) compared to the 3DPPa (x = 1231; sd = 380.1 N) and 3DPPb (x = 1029.9; sd = 166.46 N) prints. The restorations from the milled-derived group showed higher average fracture resistance than the provisional restorations obtained from the printed groups. However, the results demonstrated that all three materials analyzed in single-unit restorations are capable of withstanding the average masticatory forces.