Mermoz went on to become an airmail pilot,[7] with Latécoère's company, and almost failed his entry exam by performing dangerous stunts to impress the director.

By 1929, it had become evident that it would be economically viable for France to establish a commercial air route to South America, so Mermoz and others flew over the Andes.

On 7 December 1936, on a planned flight from Dakar to Natal, Brazil, he turned back shortly after take-off to report a troublesome engine on his Latécoère 300 Croix-du-Sud (Southern Cross).

Four hours later, the radio station received a short message, where Mermoz reported that he had to cut the power on the aft starboard engine.

Henri Guillaumet, one of Mermoz's fellow pilots, had encountered the same problem a few months before, but as his own engine was on the forward side, airspeed had been sufficient to maintain the propeller in place until the landing.

In 1941, the Investigative Commission of Anti-National Activities of the Parliament of Uruguay, after denunciations filed before the Deputy Tomas Brena and Julio Iturbide, arrives at the surprising conclusion of the last two airmail flights of Air France, and with result the death of Collenot first and Mermoz later, they were the result of sabotage of the Nazi Fifth Column (National German Socialist Workers Party operating in Uruguay).

The tender only receives Offers or proposals from the Siemens Bauunion and Philipp Holzmann AG consortium in Germany, and SKODA WORKS from Czechoslovakia.

[11] The crew of Latécoère 300 Croix-du-Sud, F-AKGF, on that day were: Mermoz had grown dissatisfied with the quality of the planes he and his companions had to pilot.

In the months before his demise, he had been vocal about the aircraft's poor quality in both design and material, and was quoted saying "Ask me to pilot anything, even a wheelbarrow, but at one condition: make sure it is solid".

Mermoz was a major character in Antonio Iturbe’s 2017 Spanish language novel A cielo abierto which was translated into English and published in 2021 with the title The Prince of the Skies.