Friction stir welding with different pin-eccentric stir tools (the pin eccentricities were 0, 0.4, and 0.8 mm, respectively) was successfully utilized for joining dissimilar aluminum alloys AA5052 and AA6061, and the influences of pin eccentricity on the microstructural evolution and mechanical properties of joints were investigated. The results showed that sound joints could be obtained by placing the hard AA6061 in the advancing side, while the welding heat input led to both the coarsening of strengthening precipitates and dynamic recrystallization and softening of the nugget zone (NZ). The application of pin eccentricity promoted the material flow in the NZ and enlarged the area of the “onion ring”. Furthermore, the average grain size and fraction of recrystallized grain in the NZ decreased as the pin eccentricity increased. All joints failed in the NZ during tensile tests, and the joint produced by the 0.8 mm-pin-eccentric stir tool performed the highest tensile strength due to the enhanced grain-boundary and dislocation strengthening.