Chemical changes and intermolecular interactions in asphalt dominate the molecular reorganization and cause the evolution of micro- and mesostructures. Given the lack of knowledge regarding the molecular chemistry-microstructure relationship of the asphalt-aggregate interface, the moisture-induced adhesive failure occurring at this interface has not been fully understood. This study investigates the multiscale structures of the asphalt-aggregate interfaces exposed to water and establishes the relationship between the structures and molecular interactions. The meso- and micromorphologies of two types of treated interfacial asphalts were observed via optical microscopy and atomic force microscopy. The results show an undulated surface and boundary retreat in asphalts because of the overall interfacial tension. Dispersed microbumps measuring tens of nanometers in height progressively grow until they merge into large bumps with increasing water exposure depending on the types of asphalt and aggregates. Fourier transform infrared (FTIR) spectrometry results show enriched polar components at the surface of the treated interfacial asphalt and water diffusion driven by complex intermolecular forces. The molecular behavior simulated by molecular dynamics calculations reveals that aliphatic molecules amalgamate into nonpolar clusters, while polar molecules migrate out and act as a surfactant to stabilize the asphalt-water system driven by the interfacial tension gradient. Internal coalescence of nonpolar components results in protrusion of the asphalt's surface, and the migration of polar components to the surface accounts for the increased absorption peaks of the polar groups. This phenomenon could explain the FTIR spectra and formation of microbumps. The state of absorbed water and nanostructures of the interfacial asphalt are dominated by intermolecular interactions among asphalt, water, and aggregates. This study provides deep insights into the structural evolution of asphalt from the chemical and molecular perspectives.