The gradient material exposure to frictional heat and plastic flow during friction stir welding leads to local variations in microstructure and mechanical properties among different joint zones. This study aims to predict strengthening contributions of local microstructural evolutions including precipitate distribution, crystal morphologies, grain size, and dislocation density for friction stir welded joints of AA2195-T6. These effects are included by a unified microstructure-sensitive physics-based constitutive modeling approach into joint local variations in yield strength, plastic hardening, and ultimate tensile strength. Local precipitate phase distributions are observed by the transmission electron microscopy method. X-ray diffraction process is conducted to measure joint local variations in dislocation density. Electron backscattered diffraction mapping is utilized to observe joint local crystal morphologies. Evolutions in the crystal slip strength due to each of mentioned microstructure attributes are inserted into a crystal plasticity finite element frame work. Modeling parameters are calibrated for AA2195-O and T6 conditions, and simulated outputs are validated by comparing with experimentally observed joint local tensile properties using the digital image correlation method. Subsequently, obtained local tensile properties in the grain scale are inserted into a macroscale global model containing all friction stir welded joint areas. An acceptable match is observed between simulated and experimentally obtained data on local and global friction stir welded joint tensile stress-strain curves and tensile failure location.