Asphalt is a widely used polymeric material in pavement engineering. However, it is easily affected by heat and ultraviolet rays, which accelerate its molecular degradation and physicochemical aging, thereby limiting its service life. To improve the anti-aging properties of asphalt, three types of nano-zinc oxide (ZnO)-modified asphalt were prepared. The chemo-rheological behavior, structural evolution of polymeric components, molecular weight distribution, and nanoscale morphology of nano-ZnO-modified asphalt were studied via dynamic shear rheometry (DSR), Fourier transform infrared spectrometry (FTIR), gel permeation chromatography (GPC) and atomic force microscopy (AFM), and the aging resistance of nano-ZnO-modified asphalt was quantitatively analyzed using the rutting factor index, functional group index, molecular size ratio, and nanoscale parameters. The findings indicate that nano-ZnO enhances the high-temperature rheological properties of asphalt and delays the increase in the rutting factor of aged asphalt. Nano-ZnO is dispersed in the asphalt matrix in the form of a physical mixture without inducing new chemical bonds, and can reduce the nanoscale roughness of asphalt. After aging, the nanoscale roughness and the aspect ratio of the bee structure decreased, and the bee structure area increased. According to the changes in the functional group index and the proportions of molecular sizes in the asphalt, it was found that nano-ZnO can significantly improve asphalt’s aging resistance. The results of this study provide insights into the nanoscale modification and structure–property relationships of polymeric asphalt binders, providing a reference for the design and application of functional polymer nanocomposite systems with improved durability.