In modern construction, the demand for sustainable and high-performance building materials is becoming increasingly urgent. One of the advanced trends is the use of alternative materials in concrete production to minimize cost and environmental impacts as well as enhance the mechanical properties and durability of concrete. This study evaluated the potential for improving the durability of concrete with high-volume fly ash (HVFC) as a cement substitution (up to 60%, 70%, and 80% by weight). The durability performance of HVFC was assessed through laboratory tests of carbonation, sulfate resistance, rapid chloride ion penetration, soluble chloride content, and corrosion activity of reinforcing steel in concrete. Results demonstrated that high-volume fly ash (FA) exhibited a positive impact on the durability of concrete. The 56-day-old HVFC specimens containing 60%, 70%, and 80% FA showed lower carbonation depth by 35%, 44%, and 57%, respectively. These values were further reduced at later ages. In addition, the incorporation of high-volume FA significantly enhanced the sulfate resistance and chloride ion penetration of HVFC as all HVFC specimens were classified in the very low chloride ion penetration group. Besides, the soluble chloride content in the 180-day-old HVFC was 70–90% lower than the soluble chloride content in the reference concrete. After 21 drying-wetting cycles, the HVFC specimens had a half-cell voltage in the range of -220 to -268 mV, which was much lower than that of the reference specimen (about -600 mV), proving a good rebar protection capability of the HVFC. The experimental results further demonstrated a great possibility of using high-volume FA to replace up to 80% cement in the production of concrete for construction applications.