Cu–Cu joints have been adopted for ultra-high density of packaging for high-end devices. However, cracks may form and propagate along the bonding interfaces during fatigue tests. In this study, Cu–Cu joints were fabricated at 300 °C by bonding 〈111〉-oriented nanotwinned Cu microbumps with 30 μm in diameter. After temperature cycling tests (TCTs) for 1000 cycles, cracks were observed to propagate along the original bonding interface. However, with additional 300 °C-1 h annealing, recrystallization and grain growth took place in the joints and thus the bonding interfaces were eliminated. The fatigue resistance of the Cu–Cu joints is enhanced significantly. Failure analysis shows that cracks propagation was retarded in the Cu joints without the original bonding interface, and the electrical resistance of the joints did not increase even after 1000 cycles of TCT. Finite element analysis was carried to simulate the stress distribution during the TCTs. The results can be correlated to the failure mechanism observed by experimental failure analysis.