The tensile deformation behaviors of laser-welded Ti-22Al-24.5Nb-0.5Mo alloy joints have been investigated at room temperature and 650 °C using in situ tensile analysis methods. The α2 phase had a significant influence on deformation behaviors of base metal at room temperature and 650 °C. The microcracks mainly nucleated in B2/α2 phase boundaries or within α2 phase and then propagated along B2/α2 phase boundaries subsequently. Compared with the plastic fracture of base metal, the fracture modes of the fully B2-phase fusion zone at room temperature and 650 °C were quasi-cleavage and intergranular fracture, respectively. While dislocation slips became foremost deformation mode in the fusion zone at room temperature, there were a great amount of slip bands on the surface of grains caused by the slip systems. The microcracks of fusion zone at 650 °C nucleated and propagated along the grain boundaries of B2 phase. Owing to the lack of grain deformation, the cross-slip bands were in small quantities on the surface of B2 phase grains.