In this work, we performed a systematic investigation of the effect of surface energy on scale formation. We made a catalogue of smooth substrates with varying surface energies by depositing self-assembled monolayers (SAMs) of functionalized coatings (organosilanes) on glass slides and exposed these substrates to a saturated aqueous solution of CaSO4. The systems reached supersaturation due to evaporation of the aqueous phase over time, resulting in CaSO4 scale formation on the substrates. We show a significant reduction in scale formation with decreasing surface energy. To determine the surface chemistry and elemental composition of the substrates, we characterized them by X-ray photoelectron spectroscopy, and the results of this study were used to explain the effect of chemistry on surface energy. Furthermore, by looking at the contribution of the substrates’ surface energy from polar and apolar components, we demonstrate that the polar component is a key factor governing scale formation on a substrate. Hence, a significant reduction in scale deposition can be achieved by minimizing the polar sites at the surface-scale interface. The proposed approach is distinctive because it studies how changing the surface properties can result in scale mitigation, whereas previous research in the field mostly have focused on developing effective chemical inhibitors to change the solid and liquid properties in the fluid phase. Our findings provide a fundamental understanding of scale formation as a function of surface energy attributes and provide insights for the design of scale-resistant surfaces with potential for technological applications.