In this study, reliable Ti2AlNb/high-Nb-containing TiAl alloy (TAN) joints were achieved by diffusion bonding. The effects of bonding temperature and holding time on the interfacial microstructure and mechanical properties were fully investigated. The interfacial structure of joints bonded at various temperatures and holding times was characterized by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS) and X-ray diffraction (XRD). The results show that the typical microstructure of the Ti2AlNb substrate/O phase/Al(Nb,Ti)2 + Ti3Al/Ti3Al/TAN substrate was obtained at 970 °C for 60 min under a pressure of 5 MPa. The formation of the O phase was earlier than the Al(Nb,Ti)2 phase when bonding temperature was relatively low. When bonding temperature was high enough, the Al(Nb,Ti)2 phase appeared earlier than the O phase. With the increase of bonding temperature and holding time, the Al(Nb,Ti)2 phase decomposed gradually. As the same time, continuous O phase layers became discontinuous and the Ti3Al phase coarsened. The maximum bonding strength of 66.1 MPa was achieved at 970 °C for 120 min.