In order to adapt to the current trend of building industrialization and solid waste recycling, a new technology of vacuum water-removal and compression was proposed in the engineering field to achieve a highly efficient pre-fabrication of machine-made sand concrete. In this study, the effect of the time of vacuum water-removal and compression treatment on the performances of machine-made sand concrete with varied initial water-to-cement ratio (W/C) was investigated. Results show that vacuum water-removal and compression can significantly improve the strength of machine-made sand concrete as compared to natural sand concrete, primarily due to the locking effect of the machine-made sand under the condition of high compaction by the treatment. The initial W/C of machine-made sand concrete decreases from 0.58 to 0.32 and the compressive strength increases by 44.6% after being treated with -0.07 MPa vacuum pressure and 15 MPa compression for 100 s. However, the improvement of performances weakens with prolonged treatment time, especially for concrete with lower W/C. Mercury intrusion porosimetry (MIP) results reveal that the porosity of concrete decreases significantly after vacuum water-removal and compression treatment. In particular, the proportion of capillary pores with pore size larger than 50 nm decreases by more than 70%. Thus, the pore size distribution is improved. The hydration degree also increases to more than 0.6. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) show that the hardened paste in concrete is densified, the amounts of aligned needle-shaped ettringite and plate-shaped Ca(OH)2 are reduced, and the bonding property of interfacial transition zone (ITZ) is improved by vacuum water-removal and compression. The machine-made sand concrete fabricated by vacuum water-removal and compression is in line with the developing trend of green, energy saving and environmental protection for the production of modern pre-cast concrete members.