The fatigue crack initiation and early propagation behavior of 2A97 Al-Li alloy was studied. The smooth specimens were fatigued at room temperature under constant maximum stress control when stress ratio (R) is 0.1 and frequency (f) is 40 Hz. Microstructure observations were examined by optical microscopy, transmission electron microscopy, scanning electron microscopy and electron back scattered diffusion, in order to investigate the relationship between microstructure and fatigue crack initiation and early propagation behavior of 2A97 alloy. The results show that the fatigue cracks are predominantly initiated at inclusions and coarsen secondary phases on the surface of 2A97 alloy. The fatigue crack early propagation behavior of 2A97 alloy is predominantly influenced by the interactions between grain structure and dislocations or persistent slip bands (PSBs). When the misorientation of two neighbouring grains is close to the orientations of the favorable slip plane within these two grains, high-angle grain boundary severely hinders the PSBs passing through, and thus leads to crack bifurcation and deflection.