In this study, the mechanical properties and permeability variation in single joint rock samples filled with a gypsum layer were investigated. In order to simulate the inclined infilled joint, the solid cylinders were saw-cut at the dip angles of 90°, 60°, 45°, 30° or 0° with respect to the samples’ axes, and then joined together with gypsum. Triaxial compression experiments with permeability measurements were then performed using these prepared samples. The results indicated that the peak strength and failure modes change with the inclined angles. In comparison with the theoretical analysis of rock with a clean joint, infilling has a marked influence on the mechanical properties to some extent. In regards to the initial permeability, the results showed decreases of approximately two orders of magnitude with the increasing of the prefabricated joint angle, and the initial permeability of the samples with a prefabricated joint were all larger than the intact sample. The evolutionary trends of the permeabilities in triaxial compression in the sandstone samples were shown to be varied with a joint filled with gypsum at different angles, due to the fact that the changes of the inner structure are quite different during the loading process.