In this study, the precipitation behavior of MnS was calculated during the solidification process of the medium sulfur, non-quenched and tempered 49 MnVS steel. And the precipitation process was directly observed by a high-temperature confocal laser scanning microscope (HT-CLSM) equipped with a gold-image furnace. Besides, the precipitated particles were proved to be MnS by using the Scanning Electron Microscope-Energy Dispersive spectroscopy (SEM-EDS) analysis. The modified thermodynamic calculation indicated that the MnS precipitated from the residual liquid steel when the product of manganese and sulfur concentrations exceeded the equilibrium value at 1417.0 °C. Meanwhile, the results calculated by FactSage software shown that the beginning precipitation temperature of MnS is about 1411.0 °C. The observation of HT-CLSM demonstrated that the primary solid on the free surface of the liquid steel was visualized at 1485.0 °C during the solidification process (cooled from 1520.0 °C to room temperature with a rate of −30 °C/min). Then, the MnS particles started to form at 1437.0 °C and rapidly grew up into shape on the solid-liquid boundary. And the precipitation of MnS continued to form in a large amount (90% of the total) in the next 10 degrees. The enrichment of Mn and S near the local melt surface may be conducive the MnS formation, which results a higher actual precipitation temperature than the calculated value.