Understanding the effects of Scandium (Sc) on the hydrogen absorption and desorption capabilities and the underlying mechanisms within Ti–Sc alloys is crucial for their applications as hydrogen storage materials. In this study, we explore the influence of Sc on deuterium (D) behavior in Titanium (Ti) films through a combination of experimental characterization and theoretical simulations. The Sc-doped Ti films with different Sc ratio were prepared using magnetron sputtering. Our findings indicate that Sc doping raises the D absorption temperature from 350 °C to 500 °C, and the Sc-doped Ti deuteride films exhibit higher apparent activation energies and temperatures for D desorption. Results from both experiments and DFT calculations indicate that these phenomena are attributed to the atomic size effect, in which the larger Sc atoms reduce the Ti–H spacing, thereby strengthening the interaction between the adjacent Ti atoms and H atoms. The enhanced interaction presents a greater challenge for H atom diffusion within α-Ti and complicates the dissociation of TiH2. This study provides a vital theoretical and experimental basis for understanding the effects of Sc doping on the hydrogen absorption and desorption properties in titanium alloys.