The exposure of cement-based materials to low-vacuum environments will result in fast moisture loss, which will cause phase transformation and pore structure changes, as well as variations in mechanical and permeability performances. In this study, a series of experiments were conducted to investigate the effects of various drying conditions (i.e., standard drying, low-vacuum drying, and oven drying conditions) on the properties of cement-based materials, including paste, mortar, and concrete. The tested properties included the mass loss during the exposure to drying conditions, as well as the compressive strength and permeability after the exposure. Results show that the drying rate of cement-based materials was higher under low-vacuum conditions than oven drying for the first two hours, but slower thereafter. Vacuum drying led to a greater enhancement in compressive strength than oven drying, with the most significant effect identified in cement paste. Additionally, oven drying showed more significant deterioration effects on permeability of cement-based materials compared to vacuum drying. The presence of aggregates in concrete has two contrasting effects on the medium permeability: intricated pathways would decrease permeability, but the microcrack formation at the interface during drying would increase permeability. Conventional two-phase material models based on the results of cement paste permeability tests cannot accurately predict the permeability of mortar or concrete after exposure to drying conditions in this study. The paper is expected to provide a basis for the investigation of the mechanical properties and durability evolution of cement-based materials under a low-vacuum environment.