To study the effect of the replacement rate of sea sand on the properties of concrete in-depth, this paper uses three kinds of original sea sands from Jiaozhou-Shandong, Zhangzhou-Fujian, and Qinzhou-Guangxi to compare and study the differences of their physical properties after mixing with river sands. Meanwhile, these sea sands were used to replace river sand with 15%, 25%, 35%, and 50% replacement rates to study their effects on the workability and mechanical properties of concrete at different ages. The test results show that: the use of sea sand in concrete basically does not affect the workability of concrete, and the sea sand with a 50% replacement rate can improve the fluidity of concrete. With the increase of sea sand replacement rate, the compressive strength and splitting tensile strength of concrete increase and then decrease, but the replacement rate has less effect on the elastic modulus; the sea sand can optimize the distribution of fine aggregate particle size and improve the strengths of concrete. However, harmful components such as shells in sea sand can adversely affect the mechanical properties of concrete at a high replacement rate. In addition, the overall effect of the sea sand replacement rate on the strength of concrete (all within 10%) is limited, and sea sand with a 50% replacement rate is still higher than the control group at long curing age. Therefore, from the engineering application point of view, the sea sand replacement rate in a range of 50% is feasible.