A computational analysis of the microstructural effect on the deformation and fracture of friction stir welded aluminum is performed. A dynamic boundary-value problem using a plane strain approximation is solved numerically by the finite difference method. The calculations take an explicit account of experimental polycrystalline microstructures typical for different weld zones, like the base material, weld nugget, and thermo-mechanically affected zones. The mechanical response of individual grains is simulated within an elastic–plastic formulation of the problem with isotropic strain hardening. A fracture model allowing for crack generation and propagation in maximum equivalent plastic strain regions is used. It is shown that the localization of plastic strain and the strength of aluminum in different weld zones are determined by the microstructure of the material on the advancing side of the weld.