Purpose:To determine and compare the fracture toughness, flexural strength and flexural modulus of four new, commercially available CAD/CAM resin composite blocks and one new CAD/CAM lithium disilicate glass-ceramic block, tested under dry and aged conditions. Materials and Methods: Three dispersed-fillers resin composite blocks, CERAS-MART, KZR-CAD-HR2, and CAMouflage NOW, one polymer-infiltrated ceramic network resin composite block, Enamic, along with Obsidian, a lithium disilicate glass-ceramic block, were characterized. Fracture toughness was determined through the notchless triangular prism specimen test, while flexural strength and flexural modulus were determined by three-point bend testing. Blocks were cut and ground to obtain (6 × 6 × 6 × 12) mm prisms and 10:1 span-to-thickness ratio bars (n = 25/group); half of the resin composite specimens were aged in 37°C distilled water for 30 days before testing. Fractured surfaces were characterized using a scanning electron microscope. Results were analyzed using Weibull statistics and two-way ANOVA, followed by Scheffé multiple means comparisons (α = 0.05). Results: With regards to fracture toughness, KZR stood out among resin composites with a dry value of 1.37 MPa·m 1/2 ; this was significantly affected by ageing, while the fracture toughness of the other dispersed-fillers resin composite blocks was not. Obsidian had the highest fracture toughness at 1.47 MPa·m 1/2 . With regards to flexural strength, Obsidian > CERASMART = KZR > CAMouflage > Enamic. The flexural strength of the resin composites was lowered by ageing. Enamic was found to have the highest flexural modulus among the resin composites (33.02 GPa), but its value was significantly lower than that of Obsidian (76.46 GPa); flexural modulus was not affected by ageing. Conclusion: There was a significant difference in flexural strength between the materials, but not unanimously in flexural modulus and fracture toughness. The tested resin composite block materials had inferior flexural strength, flexural modulus and fracture toughness compared with the tested lithium disilicate glass-ceramic block (Obsidian). Enamic, the polymer infiltrated ceramic network material, had a significantly higher flexural modulus than the dispersed-fillers materials. Ageing had a deleterious impact on the flexural strength of all RCB, while its effect on the flexural modulus was insignificant. The selection of any restorative material requires a thorough analysis of its advantages and limitations to inform the clinical decision in a case-by-case approach.