In the present study, the creep rupture behaviour and microstructural evolution of 2195-T84 Al-Li alloy are investigated at different tensile stresses. It is found that as the applied stress during the creep rupture process increases, the corresponding creep strain and creep rate significantly increase. Moreover, the evolution of microstructures, including precipitates, dislocation density and creep cavities at different stages is characterized using a transmission electron microscope (TEM), X-ray diffractometer (XRD) and scanning electron microscopy (SEM). The main strengthening precipitates are identified as T1 (Al2CuLi) and θ′ (Al2Cu) phases. Obtained results show that as the applied stress increases, T1 and θ′ phases are gradually coarsened. This coarsening is more pronounced for θ′ phase. Furthermore, the creep cavities are mainly distributed at the interface between the insoluble second phase particles and the matrix, and their average sizes gradually increase as the applied stress increases. Meanwhile, the density and size of dimples on the fracture surface gradually decrease as the applied stress increases. Moreover, the main fracture mechanism changes from transgranular dimple fracture to quasi-cleavage fracture. Based on the microstructural evolution, a novel set of unified creep rupture constitutive model is proposed. The established model incorporates the evolution of microstructures, including the dislocation density, average length of T1 and θ′ precipitates and creep cavitation, and correlates microstructural variables with creep rate. The results calculated by the constitutive model are in good agreement with the experimental data, which validates the proposed model.