The utilization of hemihydrate gypsum to produce blocks can be a more sustainable alternative to conventional cement concrete blocks. This study explores the fabrication of semi-dry gypsum-based blocks using the compression forming method to address the drawbacks associated with traditional blocks (clay block and cement concrete block) manufacturing processes, including high energy consumption and lengthy production time. However, the low mechanical strength, low water resistance, and high water absorption of gypsum-based blocks limit their application in construction. Therefore, in this study, semi-dry gypsum-based blocks were prepared using the compression forming method by investigating the interactions between the ground granulated blast-furnace slag (GGBS) content (0%, 20%, 45%), water-to-binder (w/b) ratio (0.20, 0.25, 0.30), and compaction pressure (CP) (10 MPa and 20 MPa). The compressive strength, water resistance, mineralogical composition, and microstructure of the produced gypsum-based blocks were investigated and compared with gypsum-based blocks without GGBS. It was found that adding GGBS can lead to formation of AFt and C-S-H gel when the water content reaches the required level for the reaction. These hydration products are beneficial to improve the compressive strength and water resistance. In addition, the porosity of the specimens was examined using water immersion and the mercury intrusion porosimetry (MIP) method. It was observed that when the w/b ratio is 0.25 or 0.30, a lower CP (10 MPa) should be applied. This is because higher CP (20 MPa) caused paste overflow during the forming process, resulting in undesirable pores having an adverse impact on the compressive strength. The optimal performance was obtained with GGBS content, w/b ratio, and CP at 20%, 0.25, and 10 MPa, respectively. In summary, the compression forming method could produce semi-dry gypsum-based blocks with adequate compressive strength (35.3 MPa) and water resistance (softening coefficient of 0.68).