The incompatibility of plastic deformation in a near β titanium alloy with (α + β) two phases microstructure was analyzed based on the crystal plasticity finite element (CPFE) model. The bicrystal simulation results show that the plastic deformation in the (α + β) two phases microstructure is incompatible, and the deformation behavior of α phase is significantly affected by the crystal orientation and loading direction. In addition, through coupling with three-dimensional (3D) Voronoi tessellation (VT) geometric model, the effect of globular primary α phase in the β matrix on the macroscopic mechanical response was discussed. Based on the CPFE-VT model, it is found that the incompatibility of plastic deformation between the α and β phases can result in a linear reduction of the macroscopic strength with the increase of the volume fraction of α phase. Furthermore, the distribution of primary α phase also plays an important role in the stress-strain response. The proposed model for near β titanium alloy can yield important informations for the microstructure controlling and the performance prediction.