The original synthesis of xenon tetrafluoride occurred through direct 1:5-molar-ratio combination of the elements in a nickel (Monel) vessel at 400 °C.

[9][10] Fractional sublimation (xenon tetrafluoride is particularly involatile) or other equilibria generally allow purification of the product mixture.

[9] The elements combine more selectively when γ- or UV-irradiated in a nickel container or dissolved in anhydrous hydrogen fluoride with catalytic oxygen.

That reaction is believed selective because dioxygen difluoride at standard conditions is too weak an oxidant to generate xenon(VI) species.

XeF4 reacts with the silicone to form simple gaseous products, leaving a residue of metal impurities.