A numerical simulation method based on coupling of isothermal multi-plastic deformation mechanism was put forward with isothermal forging for Ti-6Al-4V alloy as example. By investigating the plastic deformation mechanism and analyzing the strain rate sensitivity exponent m and dynamic recrystallization (DRX) of Ti-6Al-4V alloy during isothermal forging, the criteria of common plastic deformation, superplastic deformation and creep deformation were obtained. According to the criteria of the multi-plastic deformation mechanism, the real-time plastic deformation mechanism of material elements was determined and the corresponding constitutive equation was applied. This method can make simulation result more reasonable and can truly reflect the isothermal forging process of aerial materials difficult to deform: common plastic deformation, bulk superplastic deformation and isothermal pressure holding. The simulation results show that during isothermal forging process, the three kinds of plastic deformation mechanism co-exist and the deformation mechanisms of the elements change with the deformation proceeding. And the change of plastic deformation mechanism is closely related to DRX