NM450 (450 HBW-grade, low-alloy, wear-resistant steel) is an ultrahigh-strength steel, in most cases, the inclusions in NM450 have a negative effect on its toughness, strength, and weldability. However, the detrimental effect of inclusions can be reduced by inclusion modification. In this study, the effect of oxide metallurgy on the evolution of inclusions in NM450 ultrahigh-strength steel was investigated, and it was found that as the O content increased in the steel before treatment, the Ti content in the formed inclusions increased. By extending the deoxidation time after adding Ti, the ratio of inclusions smaller than 10 μm in the steel increased, whereas that of larger inclusions gradually decreased. In the Ti–Ce and Ti–Ca composite deoxidation, the former had a higher and more stable yield, but the Ca treatment was more conducive to the nucleation of sulphides, thus reflecting the oxide metallurgical effect. The addition of Ce was prone to adhesion to the crucible wall, which may have an adverse effect on actual production. This work provides a theoretical reference for broadening the scope of application of high-strength steel products, improving product quality.