A multiphysics simulation technique based on the finite element method is developed for the reliability analysis of interconnects. The multiphysics simulation characterizes multidisciplinary, including electrical, thermal, and mechanical, aspects of interconnects. It is well known that the major bottleneck preventing 3-D simulations from gaining further popularity is the computational efficiency in dealing with practically large-scale problems. To address this problem, the proposed multiphysics simulation is devised for analyzing large-scale problems with a significantly improved computational efficiency through utilizing a domain decomposition scheme called the finite element tearing and interconnecting, parallel computing, and the localized nature of thermal stresses in the interconnect structures. Both the capability and efficiency of the multiphysics simulation are demonstrated through analyzing large-scale interconnect structures including arrays of solder bumps and bonding wires. Detailed temperature distributions and localized stresses of large amplitude are obtained through the proposed simulation in a highly efficient manner.