The relationship between microstructure characteristics and fatigue properties of Ti-6Al-2Sn-4Zr-2Mo-0.1Si (Ti6242s) alloy was investigated. According to the microstructure quantitative analysis results, the solution treatments at different temperatures have an obvious effect on the proportion and morphology of primary α-phase. The changes in microstructure characteristics slightly influence the tensile property and low-cycle fatigue property of Ti6242s alloy at room temperature, whereas the dwell fatigue life and the fatigue sensitivity index are sensitive to these changes. Additionally, it is verified that the relatively strong stress concentration and inhomogeneous micro-area plastic deformation occur in the Ti6242s alloy under dwell fatigue load. Moreover, the characteristics of small plane regions and the surrounding quasi-cleavage regions in the Ti6242s alloy under dwell fatigue load at room temperature are formed through the analysis of fatigue failure fracture morphologies. The related experiment results are in good agreement with the stress-strain distribution characterizations of microstructures of equiaxed primary α-phase and the surrounding soft phase/grain. Accordingly, the relatively low inhomogeneous micro-area plastic deformation in the alloy with equiaxed primary α-phase of low volume fraction is beneficial to reduce the probability of crack initiation and can delay crack propagation, thus improving the dwell fatigue property.