The aim of this research work was to study the influence of the Friction Stir Welding process parameters while welding dissimilar AA6066 and AA1060 alloys. The effects of parameters on responses to microstructure, residual stress, hardness, and tensile strength were investigated. The Response Surface Methodology (RSM)-Box Behnken design was employed to conduct the experiments. The regression model was developed from the measured data and the adequacy of the model was also verified using ANOVA. The microstructure analysis exhibited grains sizes in heat affected zone (HAZ) and stir zone (SZ). The LCR ultrasonic testing method was used to measure the residual stress in the stirred zone of the welded samples and the results showed that compressive residual stress was generated. The weld quality has improved by optimizing the parameters of tool design, rotational speed, and welding speed using the RSM technique. The validation test was conducted to verify the predicted model, the responses exhibited improvement in the hardness and tensile strength.