The quality of extruded profiles depends largely on accurate constitutive models and thermal processing maps. In this study, a modified Arrhenius constitutive model for homogenized 2195 Al-Li alloy with multi-parameter co-compensation was developed and further enhanced the prediction accuracy of flow stresses. Through the processing map and microstructure characterization, the 2195 Al-Li alloy could be deformed optimally at the temperature range of 710~783 K and strain rate of 0.001~0.12 s−1, preventing the occurrence of local plastic flow and abnormal growth of recrystallized grains. The accuracy of the constitutive model was verified through numerical simulation of 2195 Al-Li alloy extruded profiles with large shaped cross-sections. Dynamic recrystallization occurred at different regions during the practical extrusion process, resulting in slight variations in the microstructure. The differences in microstructure were due to the varying degrees of temperature and stress experienced by the material in different regions.