Mg-Gd-Y-Zr alloy, as a typical magnesium rare-earth (Mg-RE) alloy, is gaining popularity in the advanced equipment manufacturing fields owing to its noticeable age-hardening properties and high specific strength. However, it is extremely challenging to prepare wrought components with large dimensions and complex shapes because of the poor room-temperature processability of Mg-Gd-Y-Zr alloy. Herein, we report a wire-arc directed energy deposited (DED) Mg-10.45Gd-2.27Y-0.52Zr (wt.%, GW102K) alloy with high RE content presenting a prominent combination of strength and ductility, realized by tailored nanoprecipitates through an optimized heat treatment procedure. Specifically, the solution-treated sample exhibits excellent ductility with an elongation (EL) of (14.6 ± 0.1)%, while the aging-treated sample at 200 °C for 58 h achieves an ultra-high ultimate tensile strength (UTS) of (371 ± 1.5) MPa. Besides, the aging-treated sample at 250 °C for 16 h attains a good strength-ductility synergy with a UTS of (316 ± 2.1) MPa and a EL of (8.5 ± 0.1)%. Particularly, the evolution mechanisms of precipitation response induced by various aging parameters and deformation behavior caused by nanoprecipitates type were also systematically revealed. The excellent ductility resulted from coordinating localized strains facilitated by active slip activity. And the ultra-high strength should be ascribed to the dense nano-β′ hampering dislocation motion. Additionally, the shearable nano-β1 contributed to the good strength-ductility synergy. This work thus offers insightful understanding into the nanoprecipitates manipulation and performance tailoring for the wire-arc DED preparation of large-sized Mg-Gd-Y-Zr components with complex geometries.