In order to explore the effects of different lithology and gradations of manufactured sand on concrete properties, the workability and compressive strength of three different lithological manufactured sand concrete and natural river sand concrete were carried out. In addition, the sulfate resistance of four types of concrete under the dry-wet cycle system was compared and analyzed. The results show that the workability of natural river sand concrete is better than that of manufactured sand concrete, and the workability of calcareous manufactured sand concrete is slightly better than that of siliceous manufactured sand concrete. The compressive strength of manufactured sand concrete is better than that of natural river sand concrete and the change trend of mechanical properties of manufactured sand concrete under the action of sulfate attack cycle is basically the same as that of natural river sand concrete. Under the same gradation conditions, the corrosion resistance index of manufactured sand concrete is higher than that of natural river sand concrete; the lithology of manufactured sand does not negatively affect the sulfate resistance of concrete. Well-graded manufactured sand can enhance compressive strength and sulfate resistance of concrete.