Different from conventional Mo-Si-B-based alloys consisting of Moss, Mo3Si, and Mo5SiB2, Mo3Si-free Mo-Si-B-based alloys (Moss+Mo5Si3+Mo5SiB2 or Moss+Mo5SiB2) show great potentials for more excellent oxidation resistance and elevated temperature strength. In the present work, alloying element Nb was added to Mo-12Si-10B (at.%)-based alloy to suppress the formation of the Mo3Si phase. Mo-12Si-10B-xNb (x = 10, 20, 22, 24, 26, 28, 30, and 40) bulk alloys were fabricated using mechanical alloying followed by cold pressing and then sintering at 1773 K for 2 h. Effects of Nb content on the mechanical alloying behavior and then sintered microstructure were studied. The addition of Nb with an amount less than 30 at.% accelerated the mechanical alloying process, but 40 at.% Nb addition decreased the process due to excessive cold welding and high powder volume. For the sintered bulk alloy prepared from the mechanically alloyed powders milled for 30 h, a critical Nb content between 24 and 26 at.% was found to suppress Mo3Si production and γNb5Si3 phase formed in the alloys with the addition of Nb content more than 26 at.%. Prolongation of a prior milling process could facilitate the suppression of Mo3Si and delay the formation of niobium silicides.