Traditionally, equiaxed alpha grains rather than lamellar microstructure (LM) domains in titanium alloys are regarded as potential internal crack origins in high-cycle fatigue (HCF) and very-high-cycle fatigue (VHCF) re-gimes. Here, we found that the fatigue crack is prone to initiate from a large LM domain in a titanium alloy with the composition of LM and equiaxed microstructure (EM) of fine alpha grains. Then, the mechanisms of internal crack initiation and early growth for the cases of HCF and VHCF under stress ratio R =-1, 0.1 and 0.5 were addressed and a mechanism chart was constructed to illustrate the internal cracking behavior, especially showing that the numerous cyclic pressing process dominates the related microstructure evolution with grain size refinement and nanograin formation underneath the fracture surfaces in the region of crack initiation and early growth.