The microstructure of Ti-6-4 components produced by additive manufacturing suffers from the coarse and elongated prior-β grain, which leads to a decrease of the tensile behavior and the occurrence of anisotropy. To understand and control the grain evolution, a multiscale simulation is applied to investigate the relationship between the grain selection, growth orientation, and the molten pool morphology with the different deposition layer numbers and processing parameters. The accuracy of the simulation is validated by experiments in both qualitative and quantitative ways. Results show that when the grain with unfavorable orientation loses the competitive growth with its neighbors, there will be a great chance that the blocked grain is eliminated in the following layer-and-layer deposition, which leads to the increase of the grain width. The size of the molten pool increases remarkably as the layer number increases, which lays a heavy burden on the stability of the molten pool. The analytical relationship between the molten pool morphology and the grain growth orientation is also deduced. The flat molten pool causes the grains with the direction close to the building direction to have greater survival potential. Besides, decreasing the line power energy shows little effect on the stability of the molten pool and the grain growth orientation, especially when the deposited layer number is large. The revealing mechanisms will help in understanding and further controlling the grain evolution.