O phase precipitation and variant selection in Ti–22Al–25Nb alloy during the hot shear spinning are investigated using scanning electron microscope (SEM), electron backscattered second diffraction (EBSD), and transmission electron microscope (TEM). The results show that the random O phase precipitates from the B2 matrix during the hot shear spinning. With the increase of reduction ratio, the average thickness of O precipitates increases from ≈0.18 to ≈0.50 μm. Meanwhile, the O precipitates show various morphologies, including lamella, short rod, and sphere. Twelve O variants simultaneously form in the parent B2 phase and the orientation relationship between the B2–O phases is confirmed as [−111] B2//[1–10] O and (110) B2//(001) O. Different patterns of dislocation are also found in the B2 matrix, such as dislocation tangles, dislocation nets, and dislocation arrays. They play an important role in the variant selection of O precipitates, resulting in the different angled combinations of O variants. In addition, massive dislocation piles up along the O/B2 interface and some dislocation wall generates within the O phase, which are benefit for the globularization of O precipitates.