This research aims to evaluate the mechanical properties of hot asphalt mixtures prepared using modified asphalt binders with various contents of nano-silica fume (NSF). The modification to virgin bitumen is done by shear mixing with NSF at low contents (2, 4, 6, and 8%) and high contents (20, 30, 40, and 50%) with bitumen weight. The homogeneity of the modified asphalts was assessed using Scanning Electron Microscopy. The rotational viscosity, softening point, and penetration tests were used to evaluate the rheological-physical properties of the modified asphalt binders. The stiffness, moisture damage, rutting, and fatigue of the hot mixes prepared with NSF-modified binders were evaluated using Marshall, indirect tensile strength, and double punching tests. The results showed a significant improvement in the rheological-physical properties of the modified binders with high content compared to low content of NSF. Therefore, the modified binders with 30%, 40%, and 50% of NSF were selected to prepare NSF-modified mixtures. The results showed that asphalt mixtures incorporating 30, 40, and 50% NSF-modified binders were more resistant to moisture damage, rutting, and fatigue cracking compared to the control mixture. The novelty in this research is to produce a modified asphalt mixture with two-thirds a quantity of bitumen while achieving a high performance compared to the control mixture.