Ultrasonic bonding can be of use in developing electronic packaging technology at lower temperatures to afford more reliable bonded joints. We bonded Cu and Ni sheets together and used high-temperature testing to evaluate the thermal reliability of the joints at 673 K. Furthermore, we observed the microstructure of the joint interface and evaluated its effect on the fracture load of the Cu-Ni interface. The fracture load of the Cu-Ni interface of the joints heated at 673 K temporarily increased at 300 h and then decreased after 1000 h, and the heated joints showed good thermal reliability. Obvious changes were detected in the microstructure of the interface in the heated joint. The bonded region had obviously expanded vertical to the direction of the ultrasonic bonding, and the Cu side of the joint was composed almost entirely of coarse grains because almost all the Cu grains grew during the high-temperature test. However, a finely recrystallized microstructure and a diffusion layer had formed, especially at the Cu-Ni bonding interface. We discussed the effects of the changes in the microstructure of the Cu-Ni interface and the bonding material on the fracture load of the Cu-Ni joint. The diffusion and recrystallization region was not always stronger than the Cu base metal, suggesting that expanding the bonded region is important to improve the fracture load of the Cu-Ni interface. The ratio of the unbonded region to the bonded one at the Cu-Ni interface decreased from 72 to 54 % after the high-temperature test, indicating that diffusion bonding had occurred during the high-temperature test performed at 673 K. Therefore, the fracture load of the interface between the bonded Cu and Ni was improved at 673 K.