To guide the improvement of asphalt pavement durability in airports, the effects and molecular mechanisms of jet ablation and fuel corrosion on separation failure of the asphalt-aggregate interface were investigated in this study using molecular dynamics simulations and density functional theory method. Firstly, tensile separation behaviors of the virgin, aged, and fuel-corroded asphalt-aggregate interfaces were simulated under different loading rates to evaluate their tensile strength and fatigue cracking resistance, and the experimental data were also used to verify the reliability of the simulation results. Subsequently, the molecular mechanisms of jet ablation and fuel corrosion on the separation failure of the asphalt-aggregate interface were analyzed by calculating the work of adhesion, work of cohesion, flowability parameters, and intermolecular binding energy. The results show that the aged specimen has higher ultimate tensile strength and fracture energy, but its flexibility and fatigue cracking resistance are significantly reduced. This is because the polar oxygen-containing groups generated during high-temperature aging enhance the intermolecular binding energy of the asphalt, but this also restricts the diffusion of asphalt molecules, resulting in greater frictional resistance and viscosity of asphalt during shear deformation, and thus loss of mobility and self-healing properties. On the contrary, since the light and medium oils soften and dilute the asphalt, and also weaken the intermolecular binding energy of asphalt, the fuel corrosion reduces the ultimate tensile strength and fracture energy of the asphalt-aggregate interface system, resulting in insufficient overall strength and load-bearing capacity.