Mo-base silicide alloys take advantage of their outstanding intrinsic properties, notably the high melting point and, thus, their excellent mechanical and creep strength. We demonstrate how the processing route influences the microstructure and consequently the mechanical and oxidation behaviour. Therefore two fabrication routes, a powder metallurgical (PM) and a zone melting (ZM) process, both starting from elemental powders, were used to prepare several Mo-Si-B alloys with varying chemical compositions. While PM processing leads to an ultrafine microstructure with a continuous Mo solid solution (“α-Mo”) matrix and embedded particles of the two intermetallic compounds Mo3Si and Mo5SiB2, the directionally solidified (ZM) materials possess a coarse grained structure composed of an intermetallic matrix with dendritic islands of α-Mo. A comparative assessment of the mechanical behaviour of the alloys utilizing both the Vickers indentation fracture (VIF) technique and three-point bending tests emphasizes the beneficial effect of a continuous Mo matrix resulting in increased room temperature fracture toughness and a reduction of the brittle-to-ductile-transition-temperature (BDTT). Likewise, the positive effect of the fine grained and homogeneous microstructure on oxidation performance is shown by the evaluation of mass change during heat treatment at 1100°C.