Due to the rapid development of high-speed trains, the service safety of vehicle body materials and structures has become a focal point in transport and impact engineering. Numerical simulations on the collision resistance of vehicle materials and structures are crucial for the safety assessment and optimal structural design of high-speed trains but have not been fully investigated due to the lack of damage model parameters. This study focuses on the Johnson-Cook (J-C) constitutive and damage-fracture models of a typical vehicle material, Q345C steel. A series of mechanical tests are conducted on the Q345C steel, including the quasi-static and dynamic compression/tension tests, quasi-static tension tests at different temperatures, and fracture tests along different stress paths, using the material test system and the split Hopkinson pressure/tension bar. Then, the parameters of the Johnson-Cook constitutive and damage-fracture models are calibrated based on the experimental results. In terms of the damage parameters related to stress paths, a new method of combining experiments and simulations is proposed to obtain the real, local fracture strains of the Q345C steel samples. This method allows the measurements of equivalent plastic strain and stress triaxiality histories under nonlinear stress paths, which are hardly accessible from individual experiments, and facilitates the accurate calibration of stress-path-related damage parameters. In addition, a high-speed plate penetration test is used to validate the J-C parameters, which can be directly implemented in the commercial finite element software Abaqus. The projectile trajectories from the simulation and experiment agree well with each other, demonstrating the reliability of the model parameters for impact scenarios and the efficiency of the experimental procedures utilized for calibration.