In this work, the high cycle fatigue behavior and tensile properties of Ti-Al-Mo-Cr-V-Nb-Zr-Sn titanium alloy at room temperature with a basketweave structure and bimodal structure were studied. The results show that the fatigue strength of the basketweave structure is higher, while the balance of strength and plasticity of the bimodal microstructure is better. However, the fatigue performance of the bimodal microstructure is unstable due to the bilinear phenomenon of the S-N curve. By fractographic analysis and the study of the crystal orientation, as well as the slip traces of the primary α grains and β matrix at the facets, it was found that the facets are formed on the {101¯1}<112¯0> slip system with the highest Schmid factor, and the microcracks grow along the {110}<111> slip system in the β grain, but the driving force of microcrack propagation may exceed the restriction of crystallographic orientation. Based on the conclusions above, the phenomenological models of the fatigue crack initiation mechanism of Ti-Al-Mo-Cr-V-Nb-Zr-Sn titanium alloy are established.