The space environment is subject to various cosmic rays and high-energy particles, which inevitably causes damage to space-borne equipment, posing a threat to the safety and reliability of spacecraft operation. As a critical part of interconnection in electronic components, it is of great significance to study the reliability of solder joints under radiation conditions. A combination of experimental and simulation methods was employed to study the microstructure and mechanical properties of SAC305 solder joints under 30 MeV proton irradiation, and the interaction mechanism between protons and solder joints was analyzed. The findings indicate that the high-energy protons penetrate the solder joints with little scattering and directly engage in nuclear reactions, leading to lattice defects and an increase of dislocation density. Although no defects such as voids and cracks were observed at the micron scale, the decrease of grain size at the nanoscale and the existence of cell compressive stress reduced the lattice quality and weakened interatomic bonding, resulting in a decrease of the shear strength in solder joints. At a proton fluence of 1E11 p/cm2, the shear strength of the solder joint decreased by 9.8% compared with the unirradiated state.