Plasterboard is an important building material in the construction industry because it allows for quick installation of walls, partitions, and ceilings. Although a common material, knowledge about its performance related to modern polymers and fabrication conditions is still lacking. The present work analyzes how some manufacturing factors applied during the plaster board fabrication impact on some plasterboard properties, including water absorption, flexural strength, and thermal conductivity. The manufacturing variables evaluated are the dose (D) of polymethylhydrosiloxane (PMHS), the agitation time of the mixture (H), and the drying temperature of the plaster boards after setting (T). The results suggest that factors D, H, and T induce changes in the porosity and the morphological structure of the calcium sulfate dihydrate crystals formed. Performance is evaluated at two levels of each factor following a statistical method of factorial experimental design centered on a cube. Morphological changes in the crystals of the resulting boards were evaluated with scanning electron microscopy (SEM) and the IMAGEJ image analysis program. Porosity changes were evaluated with X-ray microcomputed tomography (XMT) and 3D image analysis tools. The length-to-width ratio of the crystals decreases as it goes from low PMHS dosage to high dosage, favoring a better compaction of the plasterboard under the right stirring time and drying temperature. In contrast, the porosity generated by the incorporation of PMHS increases when going from low-level to high-level conditions and affects the maximum size of the pores being generated, with a maximum value achieved at 0.6% dosage, 40 s, and 140 °C conditions. The presence of an optimal PMHS dosage value that is approximately 0.6–1.0% is evidenced. In fact, when comparing trails without and with PMHS addition, a 10% decrease in thermal conductivity is achieved at high H (60 s) and high T (150 °C) level conditions. Water absorption decreases by more than 90% when PMHS is added, mainly due to the hydrophobic action of the PMHS. Minimum water absorption levels can be obtained at high drying temperatures. Finally, the resistance to flexion is not affected by the addition of PMHS because apparently there are two opposing forces acting: on one hand is the decrease in the length–width ratio giving more compactness, and on the other hand is the generation of pores. The maximum resistance to flexion was found around a dosage of 0.6% PMHS. In conclusion, the results suggest that the addition of PMHS, the correct agitation time of the mixture, and the drying temperature reduce the water absorption and the thermal conductivity of the gypsum boards, with no significant changes in the flexural resistance.