Inertia friction welding (IFW) is a complicated thermal-mechanical coupling process. In-depth understanding of the thermal-mechanical process can improve the joint quality. In this study, a three-dimensional (3D) thermal-mechanical coupling model was successfully established to simulate the evolution of temperature, energy density, stress, strain, and flow behavior of the IFW process between 2219-O Al alloy and 304 stainless steel. The developed model was validated by comparing it with the measured temperature and deformation. Results show a transforming distribution of interface temperature from a M-shape to a squished V-shape during the IFW process. The characterization is attributed to the transformation of the accumulated friction energy density at the interface from a M-shape to an approximate V-shape due to the combined effect of varying sliding velocity and contact pressure. The Mises stress at the region near the interface is high and low at the steel and Al alloy sides, respectively. A significant portion of the kinetic energy stored in the flywheel is dissipated in the form of plastic deformation energy and cannot be neglected. The tracer particles show that most Al alloy at the initial interface is extruded to form flash, while a small amount of Al alloy is sticky and remains at the interface center. Increasing friction pressure and initial rotation speed result in higher interface temperature, axial shortening distance, and proportion of plastic work in total energy input.