Macrosegregation, serving as a major defect in billets, can severely degrade material homogeneity. Better understanding of the physical characteristics of macrosegregation through numerical simulation could significantly contribute to the segregation control. The main purpose of this study was to predict macrosegregation in continuously cast billets with a newly developed three-dimensional macrosegregation model. The fluid flow, solidification, and solute transport in the entire billet region were solved and analyzed. Flow patterns, revealing a typical melt recirculation at the upper region of mold and thermosolutal convection at the secondary cooling zone, significantly affect the solidification and solute distribution. The solute redistribution occurring with thermosolutal convection at the solidification front contributes significantly to continued macrosegregation as solidification proceeds. The results of this study show that the equilibrium partition coefficient is mostly responsible for the magnitude of macrosegregation, while comparison between solute P and S indicated that diffusion coefficients also have some amount of influence. Typical macrosegregation patterns containing a positively segregated peak at the centerline and negatively segregated minima at either side were obtained via the proposed three-dimensional macrosegregation model, which validated by the measured surface temperatures and segregation degree.