The effects of the co-addition of Ni and Zn on the microstructure and mechanical properties of the extruded Mg-6.84Y-2.45Cu (MYC, wt%) alloy were researched. Results show that the as-cast Mg-6.79Y-1.21Cu-1.12Ni-1.25Zn (MYCNZ, wt%) alloy consists of the α-Mg, a few Y-rich phases, lamellar 18R-long period stacking ordered (LPSO) phase, and granular Mg₂(Cu, Ni, Zn) phase. After the homogenization process, phase transformation occurs in MYCNZ alloy. Some 18R-LPSO phases at the grain boundary are transformed into the thin striped 14H-LPSO phase in the grains. After extrusion, the amount, morphology, and distribution of the second phase are changed, and the grain size of the extruded MYCNZ alloy is significantly reduced to approximately 2.62 μm. Additionally, a weaker basal texture is formed in the extruded MYCNZ alloy. The tensile results indicate that the co-addition of Ni and Zn significantly enhances the tensile strength of the extruded MYC alloy while maintaining good ductility. The tensile yield strength (σ_0.2), ultimate tensile strength (σ_b), and elongation to failure (ε_L) of the extruded MYCNZ alloy are 266.9 MPa, 299.8 MPa, and 20.1%, respectively. This alloy has a good strength-plastic synergistic effect. The excellent tensile strength of the extruded MYCNZ alloy at room temperature is mainly due to grain refinement and the second phase strengthening effect, and its outstanding ductility is ascribed to the texture weakening and activation of non-basal slips.