In this paper, the mechanism on the nucleation of orientation-preferred Cu6Sn5 at different temperatures and solder compositions was investigated. Results suggest that affected by temperature and solder composition, the distribution of clusters in solder plays an important role in the formation of preferred orientation. Higher temperature, Ag element and an appropriate amount of Cu element are favorable for the nucleation of orientation-preferred Cu6Sn5. However, the increase of Cu-Sn clusters size with the increase of Cu addition will lead to the nucleation of Cu6Sn5 in liquid solder, which does not need to follow the rule of the minimal lattice mismatch between Cu6Sn5 and Cu substrate. Meanwhile, the addition of Cu and Ag is conducive to the increase of grain size. Besides, the difference in solder volume between the central and edge region results in the difference in grain orientation. Furthermore, a model is established to illustrate that how the reflow temperature, Cu and Ag content affect the nucleation of orientation-preferred Cu6Sn5 through affecting the cluster evolution. The results have significant meaning in understanding and controlling the formation of Cu6Sn5 preferred orientation and improving the reliability of solder joints.