In order to understand the modify mechanical properties and durability of cement-based materials with low water-binder ratio, the cement-based materials were prepared with 0.5%~4% nano-CuO, and the influence and mechanism on setting time, liquidity, mechanical properties, and durability were analyzed. The results showed that 0.5%~4.0% nano-CuO could reduce the setting time and liquidity of cement-based materials. The bigger the dosage, the more the lower amplitude. 1%~4.0% nano-CuO could improve the flexural strength and compressive strength of cement-based materials, and reduce the drying shrinkage and permeability of cement-based materials, with 2% the best. Although nano-CuO could not participate in the secondary hydration of cement, it did promote the hydration of cement; Through comprehensive analysis, we found that nano-CuO can exert size effect, filling effect of micro-aggregate and surface activity effect, which can achieve the purpose of improving the compactness of cement-based materials and refining pore structure. Therefore, we conclude that nano-CuO can modify the mechanical properties and durability of cement-based materials to a certain extent after replacing cement.