Knowledge on durability of concrete/epoxy bonded systems is becoming essential as the use of these systems in applications such as fiber-reinforced polymer (FRP) in strengthening of concrete structures is becoming increasingly popular. Prior research studies in this area indicate that moisture plays an important role on durability of these systems. Premature failures of the bonded system may occur regardless of the durability of the individual constituent materials forming the material system, and that the durability of the overall FRP-bonded system may be governed by the interface integrity. In this study, fracture toughness of concrete/epoxy interfaces as affected by combinations of various degrees of moisture ingress and temperature levels is quantified. For this purpose, sandwiched beam specimens containing concrete/epoxy interfaces were tested and analyzed using the concepts of fracture mechanics. Mechanical properties of individual materials constituting the interface (concrete and epoxy) were also characterized for the evaluation of the corresponding interface fracture toughness. Experimental results have shown a significant decrease, up to about 50%, in the interface fracture toughness of concrete/epoxy bond with selected levels of moisture and temperature conditioning of the specimens for both mode I and mixed mode conditions, and that moisture affected debonding may occur in the interface region involving a distinctive dry-to-wet debonding mode shift from material decohesion (concrete delamination) to interface separation. The mechanistic knowledge and the experimental data presented in this paper will serve as a basis for the use in the design improvement of material systems containing such interfaces for better system durability.