The reliability of friction stir welded joints is a critical concern, particularly given their potential applications in the aerospace manufacturing industry. This study offers a quasi-in situ observation of the microstructural response during fatigue crack growth (FCG) of a friction stir welded AA2024-T4 joint, aiming to correlate fatigue crack growth behavior with mechanical properties investigated using electron backscatter diffraction (EBSD). Notched compact tension (CT) specimens corresponding to the morphology of the stir zone (SZ), advancing side (AS), and retreating side (RS) were meticulously designed. The findings indicate that the welding process enhances the joint’s resistance to fatigue crack growth, with the base metal exhibiting a shorter fatigue life (i.e., ~105 cycles) compared to the welding zones (SZ ~ 3.5 × 105 cycles, AS ~ 2.5 × 105 cycles, and RS ~ 3.0 × 105 cycles). Crack propagation occurs within the stir zone, traversing refined grains, which primarily contribute to the highest fatigue life and lowest FCG rate. Additionally, cracks initiate in AS and RS, subsequently expanding into the base metal. Moreover, the study reveals a significant release of residual strain at the joint, particularly notable in the Structural-CT-RS (Str-CT-RS) sample compared to the Str-CT-AS sample during the FCG process. Consequently, the FCG rate of Str-CT-AS is higher than that of Str-CT-RS. These findings have significant implications for improving the reliability and performance of aerospace components.