Investigations into effects of humidity and oxygen on a polymer-bonded MoS2-based dry film lubricant (DFL) coating, on grit-blasted Ti–6Al–4V using a cylinder-on-flat configuration, are reported. Sustained low friction and low wear occurred in both low-humidity air and low-humidity argon, producing significant extension of fretting wear lifetimes. A cracked-paved structure was observed in low-humidity air which was not observed in low-humidity argon. The Mo-DFL coatings were observed to be highly sensitive to humidity. As humidity increased, a notable rise of friction and wear ensued which reduced the system lifetime. Different friction evolution was observed in high-humidity air and high-humidity argon before failure, with a short-lived but established low friction phase in high-humidity air and a consistent high friction phase in high-humidity argon. Although oxidation of the MoS2 to MoO3 is a key process of degradation of DFLs of this type, this oxidation reaction does not operate in the absence of humidity.