The chemical reactivity of single crystals of binary and ternary bismuth chalcogenides toward oxygen, water, and carbon monoxide has been investigated by X-ray photoemission spectroscopy by using synchrotron radiation. We find that single crystals of Bi2Se3 are inert toward oxygen in the temperature range 300–550 K. The protection against surface oxidation at high temperature is important for preserving the thermoelectric efficiency in applications for power generation. By contrast, water adsorbs at room temperature on Bi2Se3. Finally, we find a different reactivity toward carbon monoxide in PbBi6Te10 at room temperature with respect to other bismuth chalcogenides.