This work thoroughly examined the microstructure evolutions of the cast Ti–45Al–2Nb–2Cr-0.3C alloy after multi-stage heat treatments, involving solid solution, cyclic quenching and isothermal annealing. The experimental findings revealed that solid solution and isothermal annealing processes decreased the lattice constants of component parameters, while the cyclic quenching resulted in the lattice expansion. The blocky (B2+γ) phases, which had been distributed along the colony boundary of the as-cast microstructure, disappeared after multi-stage heat treatment, and the lamellae showed a trend of thinning first and then thickening. In addition, the cyclic quenching process resulted in a large number of dislocations and stacking faults within γ lamellae. These crystal defects could act as heterogeneous nucleation sites, lowering the energy barrier of Ti2AlC precipitated from the lamellar matrix during the isothermal annealing stage. The dispersed Ti2AlC particles, with an average size of 45 ± 15 nm, showed the following coherent relationship with the lamellar matrix, [1‾216‾]Ti2AlC//[001]γ and (101‾0)Ti2AlC//(2‾20)γ.