Manufactured sand is one of the effective ways to alleviate the extreme shortage of natural sand in the construction industry. This paper uses granite and limestone manufactured sand to study the effect of high fines content on the durability of high-strength manufactured sand concrete, and analyzes its influence mechanism by combining macro and micro test methods. The results show that the carbonation depth of manufactured sand concrete is the smallest when the fines content is 10%. When the fines content is less than 15%, the chloride and sulfate impermeability of concrete are improved effectively. Through macroscopic and microscopic tests, it is found that the main reason why fines can improve the durability of concrete is the filling effect. Too much fines will inhibit the hydration of cement and adversely affect the durability of concrete. Therefore, the fines content of high-strength manufactured sand concrete should be controlled within 5~15%, and the durability is the best when the fines content is 10%.