Officials did not specify the exact roles of the unidentified diplomats, one of whom suffered a fall, forcing the other to seek help from the US embassy.
"In coordination with Mexico's mountain rescue brigade and the United States embassy, action is being taken to rescue two diplomats missing on Citlaltepetl," the civil protection authority for the state of Puebla said in a statement.
"They did not advise any authorities, municipal or state, about the route or date of their ascent," a local government source told AFP, speaking on condition of anonymity.
Emergency personnel set off on foot to camp with them and wait until conditions improved -- or failing that, to evacuate the injured climber on stretcher.
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Best known as Pico de Orizaba, the 5,610-meter (18,400- foot) mountain on the border between the states of Puebla and Veracruz attracts professional climbers from around the world as well as poorly-equipped amateurs.
Last November, authorities recovered the body of an American mountaineer from the same summit, following a risky rescue operation which injured one worker.
In 2015, the mountain gained notoriety following the discovery of two unidentified mummified bodies at an elevation of 5,200 meters -- which have not been recovered due to their precarious location -- and a third which is now in a local museum.