<p>This study designed a laboratory experiment to investigate steel–slag reaction and quantify the reactivity between high-Ti steel (0.47 and 2.56 wt pct) and CaO–SiO₂-based continuous casting mold flux. Thermodynamic calculations and molecular dynamics (MD) simulations were integrated to analyze the effect of the reaction on slag properties in detail. Results indicated that molybdenum alloy crucibles could resist dissolution by steel and remain stable in slag, making them ideal for contact experiments. At 0.47 wt pct [Ti], the (SiO₂) content in slag decreased by 5.02 wt pct, while (TiO₂) increased by 5.57 wt pct; changes in other components were within 1 wt pct. The viscosity at 1300 °C remained stable at 0.42 Pa·s, while the melting and break temperatures increased by 29 °C and 36 °C, respectively. When [Ti] increased 2.56 wt pct, (SiO₂) decreased by 24.82 wt pct, and (TiO₂) increased by 29.76 wt pct; (Na₂O) and (Li₂O) decreased by 3.05 wt pct and 1.51 wt pct, respectively. The slag viscosity dropped significantly from 0.42 to 0.12 Pa·s, and its crystallization was notably enhanced. High-melting-point perovskite (CaTiO₃) precipitated from the liquid slag during cooling. MD simulations revealed that increasing the TiO₂/SiO₂ mass ratios led to a structural transformation from Si–O–Si to Si–O–Ti and Ti–O–Ti bonds. This disrupted the network structure and enlarged network gaps, resulting in a sharp decline in viscosity. Overall, the study demonstrated that [Ti] in high-Ti steel mainly reacts with (SiO₂) in the mold flux, and higher [Ti] levels intensified this reaction. This reduced the stability of flux’s melting behavior and crystallization properties, negatively impacting the continuous casting process and the surface quality of slabs. Therefore, developing low-reaction mold fluxes toward high-Ti steels is a key direction for future research.</p>