In this work, a high-quality Mg-2.85Nd-0.25Zn-0.5Zr (wt%) alloy ingot with a diameter of 280 mm was successfully fabricated by direct chill casting. There was no obvious composition segregation along the radial direction of the ingot. The large temperature gradient along the radial direction, accurately the higher cooling rate in the surface, gives rise to both grain size and eutectic compounds fraction to gradually decrease from the center to the surface. This results in varying mechanical properties at different positions, such as higher strength and ductility in the surface than in other positions. The peak-aged alloy exhibited a higher strength-ductility synergy, with tensile strength of 282 MPa and elongation of 12.5%, than other Mg-Nd based alloys processed by permanent mold casting and sand casting. Furthermore, it is worth noting that the peak-aged alloy manifested significant strain hardening and high heat resistance, as evidenced by liner strain hardening at temperatures between 100 and 250 °C, which is mostly due to stable solute hardening triggered by the large atomic radius of Nd atoms in the α-Mg matrix. These findings provide references for the application and manufacture of large-scale magnesium alloy ingots. • A high-quality Mg-2.85Nd-0.25Zn-0.5Zr (wt%) alloy ingot with a diameter of 280 mm was successfully fabricated by direct chill casting. • The fraction of eutectic compounds increases and the grain size decreases from the center to the surface. • The alloy exhibited higher strength-ductility synergy than other Mg-Nd based alloys processed by permanent mold casting and sand casting. • The alloy showed abnormal strain hardening at high temperatures, rather than strain softening.