The microstructural features of high-temperature titanium alloy Ti650 and their effects on mechanical properties were investigated. Results indicate that the S2-type (Ti,Zr)₆Si₃ silicide precipitates in the alloy exhibit no specific crystallographic orientation relationship with the matrix. Their morphology and distribution strongly depend on the microstructure type: in fine-lamellar Widmanst?tten structure, fine elliptical particles (20–60 nm) precipitate along the α/β interface; while in equiaxed, dual-phase, or coarse-lamellar Widmanst?tten structures, blocky silicides (approximately 200 nm) form within α grains. Room-temperature tensile tests reveal that equiaxed and dual-phase microstructures achieve the optimal strength-ductility balance (tensile strength of approximately 1100 MPa, elongation of approximately 13%). The fine-lamellar structure exhibits outstanding creep resistance at 650 °C and 100 MPa, with a steady-state creep rate nearly one order of magnitude lower than that of the equiaxed structure. Further mechanism analysis indicates that in the equiaxed structure, dislocations can traverse coarse silicide grains within the crystal via bypass mechanisms, allowing the creep process to persist. In contrast, fine spherical silicides are uniformly distributed within the lamellae and at grain boundaries. These silicides synergistically strengthen the lamellar structure, significantly increasing the energy barrier to dislocation motion and thereby conferring superior creep resistance on this microstructure.