By means of creep properties measurement and microstructure observation, the deformation and damage behavior of an as-cast TiAl-Nb alloy during creep at temperature near 750 °C were investigated. The results showed that the microstructure of the alloy consisted of lamellar γ/α2 phase, and the boundaries consisted of γ phase located in between lamellar γ/α2 phases with different orientations. In the latter stage of creep, the dislocation networks appeared in the interfaces of lamellar γ/α2 phases due to the coarsening of them, which made the coherent interface transforming into the semi-coherent one for reducing its adhesive strength. The deformation mechanism of the alloy during creep was twinning and dislocations slipping within lamellar γ/α2 phases. In the later period of creep, significant amount of dislocations plied up in the interfaces of lamellar γ/α2 phases, which may cause the stress concentration to promote the initiation and propagation of the cracks along the lamellar γ/ α2 interfaces perpendicular to the stress axis. Wherein, some cracks on the various cross-sections were connected by tearing edge along the direction of maximum shear stress, up to the creep fracture, which is considered to be the damage and fracture mechanism of alloy during creep at 750 °C.