Aim: To carry out a comparative evaluation of flexural strength and impact strength of computer-aided design/computer-aided manufacturing (CAD/CAM) denture base resin with conventional heat cure resin fabricated by two different techniques. Materials and methods: The study was carried out in three groups based on the manufacturing process of the dentures: Group I (n = 30)—control group containing specimens fabricated by conventional pressure-pack technique (polymer and monomer—powder and liquid, (DPI, Mumbai, India)); Group II (n = 30)—specimens fabricated using injection molding technique (SR—Ivocap High Impact, Ivoclar Vivadent, Liechtenstein); and Group III (n = 30)—specimens fabricated using CAD/CAM technology (Bloomden™, China). The values for flexural strength of each specimen were measured using a universal testing machine by a three-point bending test. Impact strength testing of the samples was done on the Izod impact testing machine with a pendulum of S2 scale in air at 23 ± 2°C. The mean values of the flexural strength and impact strength were calculated by the one-way ANOVA test and intergroup comparison was done using Tukey pairwise comparisons. Results: The flexural strength (FS) and impact strength (IS) of CAD/CAM (FS = 93.16 ± 5.46 MPa and IS = 15.625 ± 2.512 kJ/m²) samples were highest followed by injection molded samples (FS = 84.82 ± 5.30 MPa and IS = 12.511 ± 2.908 kJ/m²) and least for compression molded control group (FS = 74.70 ± 5.02 MPa and IS = 8.446 ± 0.937 kJ/m²). Conclusion: CAD/CAM denture base resins have the highest flexural and impact strength compared to injection molded and compression molded heat cure denture base resins.