Commercially pure (CP) titanium is thermally processed and subjected to biaxial stress. However, the evolution of the microstructural deformation mechanisms under such circumstances is not adequately understood. In this study, the mechanical responses and microstructural deformation mechanisms of TA2 CP titanium sheets under equi-biaxial loading at room temperature (RT), 300 °C, and 400 °C were studied. The activated slip and twinning systems were investigated by transmission electron microscopy (TEM) after polished cruciform specimens were biaxially tensile-tested at RT and elevated temperatures. The results show that {112¯2} contraction twinning and {101¯2} extension twinning are the main deformation mechanisms of RT biaxial deformation, while dislocation glide is predominant in biaxial deformation at 300 °C and 400 °C. This difference yields varied work-hardening behaviors at RT and elevated temperatures. In biaxial deformation at 400 °C, the main slip trace type is multiple slip. The interaction of different slip systems in multiple slip created shear deformation concentration areas and further induced cross-slip. However, in biaxial deformation at 300 °C, the amounts of simplex and multiple slip were significantly reduced compared to those at 400 °C because the lower temperature increased the critical resolved shear stress and insufficient activated slip systems were available for grain deformation. Therefore, several stress-concentration areas were generated with the activation of cross-slip.