Electrodeposited <111>-oriented nanotwinned Cu (NT-Cu) films consist of micron-scale columnar grains and they are thermally stable up to 400 °C. By adding nanoscale equiaxed Cu grains at the bottom of the NT-Cu films, anisotropic large grain growth could be triggered below 200 °C. The grains grew over 50 μm in bonded Cu–Cu films with 5.7 μm thick. Two main factors are identified for the low thermal stability and large grain growth behavior. The grain refining and transition layer thickening are effective to lower the thermal stability of the NT-Cu and reduce the required temperature for recrystallization and grain growth in the NT-Cu film. By increasing the fine-grained layer and refining the grain size of the columnar twinned grains, anisotropic grain growth can occur at 150 °C. The low thermal stability NT-Cu can be employed to completely eliminate the bonding interface at low temperatures in Cu–Cu joints. However, when the fine-grained layer is thicker than a threshold value, normal grain takes place and the bonding interface remains. The mechanism of anisotropic large grain growth was also proposed.