Aluminum 6061-T6 sheets with a Ti–6Al–4V titanium alloy interlayer were investigated using friction stir welding (FSW) to achieve strong bonding. The influence of welding parameters on welding quality and strength was assessed by varying rotational speeds and traverse speeds, the optimal welding conditions. Welded samples with a cross section of 28 mm and excellent surface smoothness were prepared and analyzed to measure the residual stress using X-ray diffraction (XRD) techniques. This study investigated the effect of tool geometry and type on residual stresses in welded specimens and highlighted the importance of choosing the appropriate tool geometry and type to minimize residual stresses. Furthermore, finite element simulation of the FSW process was conducted using a thermal modeling approach to calculate the heat generated and predict residual stresses using ABAQUS software. Comparison of the residual stress values obtained from numerical simulations with experimental measurements demonstrated the model’s ability to predict residual stresses in FSW adequately. The experimental and numerical results revealed that an increase in rotational speed and tool feeding led to higher stresses in the welded region due to an increased thermal gradient. Examination of the microstructure shows that during the welding process, the weld cross-section has become smaller than the base metal. The ultimate tensile strength and microhardness obtained in optimal conditions were 245 MPa and 108.2 HV, respectively. Examining the fracture surfaces from the tensile tests showed the soft fracture type, which is characterized by the presence of holes and depressions in the three-layer sheet.