With an aim to develop novel Cu–Zn alloys with high mechanical properties, in this study, Ni and Si elements were added to Cu–10Zn and Cu–20Zn alloys, and four kinds of Cu–Zn alloys were synthesized through gravity casting. The effect of the addition of Ni and Si on the microstructure and mechanical properties has been systematically investigated. Results revealed that the addition of Ni and Si not only refined the microstructure but also played significant roles to improve the mechanical properties of Cu–Zn alloys; δ-Ni2Si precipitates were formed in the Cu–20Zn–1.5Ni–0.34Si alloy, which obeyed a crystal orientation relationship of (001)Cu‖(001)δ and Cu‖δ. As compared with the Cu–20Zn alloy, the tensile strength of the studied Cu–20Zn–1.5Ni–0.34Si alloy was increased from 373.2 MPa to 776.4 MPa, and the yield strength increased from 242.1 MPa to 718.4 MPa. Operative strengthening mechanisms in the Cu–20Zn–1.5Ni–0.34Si alloy with different thermal-mechanical treatment states will be discussed in detail with the aim to draw a new strategy to develop high strength brass alloys.