The first results on the activation process and mechanisms of novel quinary alloy Ti-Zr-V-Hf-Nb non-evaporable getter (NEG) film coatings with copper substrates were presented. About 1.075 µm of Ti-Zr-V-Hf-Nb NEG film coating was deposited on the copper substrates by using the DC sputtering method. The NEG activation at 100, 150, and 180 °C, respectively, for 2 h was in situ characterized by x-ray photoelectron spectroscopy (XPS). The as-deposited NEG film mainly comprised the high valence state metallic oxides and the sub-oxides, as well as a small number of metals. The in situ XPS studies indicated that the concentrations of the high-oxidized states of Ti, Zr, V, Hf, and Nb gradually decreased and that of the lower valence metallic oxides and metallic states increased in steps, when the activation temperature increased from 100 to 180 °C. This outcome manifested that these novel quinary alloy Ti-Zr-V-Hf-Nb NEG film coatings could be activated and used for producing ultra-high vacuum.