Mechanical activation of solids leads to an increased internal energy caused by the introduction of defects. This can result for example in a reduced surface melting temperature of activated particles, which in turn may affect their sintering behavior. Analogously the spreading behavior of MoO3 over Al2O3 may depend on the mechanical treatment during physically mixing the solids. Differences in the spreading over Al2O3 of unmilled MoO3 and MoO3 that was mechanically activated for 600 min were investigated by SEM/TEM, XPS, ESR, and in situ high-temperature Raman spectroscopy. SEM and EDX analyses of these physical mixtures make surface melting during the calcination very probable. In addition, analysis of XPS spectra also shows that spreading occurs under these conditions. However, spreading in the mixture with milled MoO3 is more effective. ESR spectroscopy shows that Mo5+ centers are reoxidized after calcining the mixtures with unmilled MoO3 in moist oxygen. For the mixture with milled MoO3 an additionally observed Mo5+ species in C-2 upsilon distorted sixfold coordination is stable against oxygen for many hours, independent of the presence or absence of water. This higher stability of this defect species against reoxidation is attributed to an improved stabilizing effect of the Al2O3 support due to a pronounced spreading of mechanically activated MoO3. High-temperature Raman spectroscopy of pure, unmilled MoO3 reveals that a transformation into polymeric species occurs at temperatures above 948 K. At 1053 K, melting is observed and the Raman bands of crystalline MoO3 are lost. Calcination of an unmilled physical mixture of 9 wt % MoO3 and Al2O3 at the considerably lower temperature of 823 K in dry O-2 leads to the observation of Raman bands of an amorphous polymeric Mo surface melt. Quenching this sample to room temperature results in a Raman spectrum which is attributed to a glassy surface MoO3 phase. Calcination of the physical mixture milled for 3 h at 823 K also leads to a Raman spectrum of the surface melt. Quenching to 298 K does not lead to a considerable change of the spectrum, this being explained by a more effective spreading of the Mo phase in the mechanically activated mixture. This surface Mo phase is highly reactive toward H2O during rehydration at 298 K, which leads to the formation of a polymeric surface species. A long time spreading experiment at 723 K reveals that this process is considerably slower and less effective at this lower temperature.