Among the recent research Friction-Stir-Welding (FSW) has been adopted worldwide as one of the dominant processes for welding lightweight aerospace Aluminum alloys. Al-2195 which is one of the new generation Aluminum alloys has been used in the external tank of the space shuttles. Aerospace fabricators are continuously pursuing FSW-technologies in its efforts to advance fabrication of the external tanks of the space shuttles. The future launch vehicles with reusable mandates require the structures to have excellent fatigue properties and improved fatigue lives. The butt-welded specimens of Al-2195 and Al-2219 are fatigue tested according to ASTM-E647. The effects of stress ratios, use of corrosion preventive compound (CPC), and the applications of periodic overloading on fatigue lives are investigated in this study. Scanning-electron-microscopy (SEM) is used to examine the criticality of the failure surfaces and the different modes of crack propagation that could have been initiated into the materials. It is found that fatigue life increases with the increase in stress ratio, and results show an increase in fatigue life ranging over 30% with the use of CPC, and the fatigue life increases even further with periodic overloading; whereas crack-closure phenomenon predominates the fatigue fracture. Fracture mechanics analysis and crack similitude was modified for fatigue cracks by Paris. Numerical studies using FEA has produced a model for fatigue life prediction scheme for these structures, where a novel strategy of the interface element technique with critical bonding strength criterion for formation of new fracture surfaces has been used to model fatigue crack propagation lives. The linear elastic fracture mechanics stress intensity factor is calculated using FEA and the fatigue life predictions made using this method are within 10–20% of the experimental fatigue life data obtained. This method overcomes the limitation of the traditional node-release scheme and closely matches the physics of the crack propagation.