In this work, we studied the effect of the reaction between the depositing atoms and the substrate element on the morphological evolution of the each deposition of the Sn–Bi–Sn multilayer structure on the Cu substrate. For the deposition of the single Sn layer on the Cu substrate, the reaction between the depositing Sn atoms and the Cu substrate is very minimal. TEM study shows only a very thin interfacial Cu–Sn compound layer (17 nm) formed between the depositing Sn layer and the Cu substrate. Yet, the latent heat of the vaporized Sn (296.1 kJ/mol) melts the Sn deposition layer on the Cu layer. Owing to the surface tension of the molten Sn, the molten Sn could agglomerate as the Sn clusters for reducing the surface energy. For the subsequent deposition of Bi and Sn layers, the eutectic reaction would occur between the depositing Bi atoms and the Sn clusters. The energy required for the eutectic reaction between the depositing atoms and the substrate elements is provided by the latent heat released from the vaporized Bi (or Sn) atoms arriving on the deposition surface. The eutectic liquid formed on the deposition surface serves as a medium to (1) receive and redistribute the depositing atoms and (2) dissolve and transport the substrate elements. The above process (1) and (2) explain the morphological evolution of the each deposition of the Sn–Bi–Sn multilayer structure and the mechanism of morphological evolution is proposed in this work.