The capabilities of Additive Manufacturing (AM) techniques have grown rapidly in recent years, however, current available metal powders for AM processes, such as Powder Bed Fusion and Directed Energy Deposition, are limited and primarily fabricated through gas atomization process which; the gas atomization process is capable of producing metal powders 15 µm to 150 µm in size with near spherical shape. Despite the advantages of atomization process, iron or nickel-based Oxide Dispersion Strengthened (ODS) powders, with nanocrystalline microstructure, cannot be produced with the gas atomization process because of the high melting temperature of yttrium (III) oxide (Y2O3, 2425 °C) compared to iron (Fe, 1538 °C), nickel (Ni, 1668 °C), chromium (Cr, 1907 °C) and aluminum (Al, 660 °C), thus, uniform dispersion of Y2O3 is problematic for ODS powders. In this work, a combination of Mechano-Chemical Bonding (MCB) process and Mechanical Alloying (MA) by planetary ball milling (BM) will be implemented to produce ODS powders suitable for AM applications. The MCB process fractures and uniformly disperse the Y2O3 nanoparticles and the nanoparticles are bonded on the surface of the master particles (Ni and Cr). Also, the MA process, because of the constant fracturing and cold-welding of the elemental particles, produces alloyed ODS powders with suitable uniform size distribution, near spherical shape, and nanocrystalline microstructure. The objectives of this research are to (1) optimize the MCB+BM processing parameters and (2) study effects of the process parameters on the size, morphology, and microstructure of Ni-based ODS powders for metal AM applications using Laser Engineering Net Shaping (LENS) machine. Results showed that Ni-based ODS particles with nearly spherical in morphology, average particle size of 15 μm, uniform dispersion of Y2O3, and nanocrystalline microstructure can be successfully produced via the proposed MCB + BM methodology. These resultant Ni-based ODS particles were successfully used on a LENS AM machine to produce coupon specimen. The coupon specimen microstructure contains γ-NiAl matrix and submicron γ'-Ni3Al strengthening phase.