The engine thrust chamber, which consists of an electroformed nickel (Ni) outer wall and a copper-zirconium alloy (Cu-Zr alloy) inner wall, is widely used in the aerospace field. With regenerative cooling technology, the Cu-Zr alloy wall is milled with grooves through which the low-temperature fuels of liquid hydrogen and oxygen can flow to absorb heat in the chamber. When joining the thrust chamber with other parts by arc welding, the Ni/Cu-Zr alloy interfacial bonding strength decreases because of the high temperature, and large welding stress may occur at the interface, resulting in debonding. In this study, the interfacial bonding strength between the electroformed Ni and the Cu-Zr alloy was measured at different temperatures, and the thermal and mechanical processes of the Ni/Cu-Zr alloy interface during welding with different parameters were investigated by numerical simulation. Tensile test results show that the Ni/Cu-Zr alloy interfacial bonding strength decreases significantly with the increase in temperature, resulting from the microstructural deterioration of the Cu layer at the interface. The model calculation results show that the interface temperature exceeds 700 degrees C due to the welding heat input, and a significant stress concentration occurs on Cu-Zr alloy rib edges near the weld, leading to debonding. Reducing welding power and adjusting welding speed may result in insufficient Ni penetration, and the debonding tendency still exists. It is found that precisely adjusting the welding heat input while enhancing the inner wall heat conduction by a water-cooling fixture can prevent the Ni/Cu-Zr alloy interface from debonding and ensure the weld quality.