Cu-Zn based alloys have been widely used in various applications due to their outstanding properties, such as high electrical conductivity and increased hardness over pure Cu. The thermal effect during electrical conduction leads to the requirement of excellent thermal stability for maintaining performance, which is strongly related to the microstructural transformation and kinetics. However, the atomic-scale microstructural evolution of Cu-Zn systems has scarcely been discussed. In this study, the reaction process of Cu-Zn systems was observed via in situ high-resolution transmission electron microscopy (in situ HRTEM). The Zn/Cu thin films were converted to β-CuZn at 180 ℃ and exhibited an epitaxial relationship with Cu, which was described as (01 1¯)β-CuZn // (1¯11)Cu and [1 0 0]β-CuZn // [1 1 0]Cu. Subsequently, the Cu-rich solid solution (α phase) was formed at 300 ℃ to decrease the Gibbs free energy, where layer-by-layer diffusion took place on the (1¯1¯ 1) plane. Based on the improved twinnability of the α phase with decreasing stacking fault energy (SFE), nanotwins grew along with the α phase. The twin boundaries effectively retard atomic migration, which is expected to optimize the mechanical properties. The fundamental science described in this study provides novel insights into Cu-Zn alloys, which could be explored in a wide range of alloy systems.