15-5PH stainless steel castings are key components in fracturing trucks. However, DS-type inclusions can lead to fatigue failure of the material. To elucidate the formation mechanism of large-size DS-type inclusions, the evolution, growth, and aggregation of inclusions during vacuum oxygen decarburization, ladle refining, and vacuum casting were studied. The results show that the DS-type inclusions with sizes larger than 20 μm were CaO–Al2O3–SiO2–MgO–CaS composite inclusions. After Si–Al additions in vacuum degassing, typical inclusions were spinel or Al2O3. After Ca–Si additions during ladle treatment, typical inclusions were liquid or dual-phase Al2O3–CaO–SiO2–MgO. During the solidification process, due to the segregation of S and the decrease in solubility, the typical inclusions in the final casting became Al2O3–CaO–SiO2–MgO–CaS. For optimal fatigue performance of stainless steel castings, slag and refractory composition control were also necessary because the [Mg] contents mainly come from the slag and lining.