The stress–strain response of sintered silver nanoparticles (AgNP) materials is precisely characterized in order to adapt for numerical analysis and rational design of electronic packaging structures in this study. A framework of crystal plasticity finite element method (CPFEM) is established based on the mechanism of crystal plastic deformation to describe the mesoscopic structural influence of grain evolution on the macroscopic properties of sintered AgNP materials. Material parameters of crystal plasticity are defined and initial orientations are randomly assigned for sintered AgNP grains. To calibrate the mesoscopic mechanical properties of sintered AgNP by the proposed CPFEM, the results of CPFEM simulations and uniaxial tensile tests subjected to different strain rates and temperatures are compared in terms of the stress–strain curves as the critical macroscopic characteristics. The predicted stress and deformation distributions in the polycrystalline structure demonstrate that the significant inhomogeneity of stress and deformation is caused by the different grain orientations of sintered AgNP. Furthermore, we elucidate the fracture mechanism influenced by the temperature and strain rate and also the effect of initial crystal orientation on the plastic strain of sintered AgNP. This study sheds light on the morphology design of sintered AgNP with optimized mechanical properties and fatigue resistance.