Antoniadi was born in Constantinople (now Istanbul, Turkey). He established quite early a reputation as a brilliant observer and in 1893 was invited by Camille Flammarion to work at his observatory at Juvisy near Paris. From 1909 he worked mainly with the 33-inch (84-cm) refracting telescope at the observatory at Meudon. He became a French citizen in 1928.

In his two works La Planète Mars (1930) and La Planète Mercure (1934), Antoniadi published the results of many years' observations and presented the best maps of Mars and Mercury to appear until the space probes of recent times. With regard to Mars he took the strong line: “Nobody has ever seen a genuine canal on Mars,” attributing the “completely illusory canals,” seen by astronomers such as Percival Lowell and Flammarion, to irregular natural features of the Martian surface. Antoniadi also observed the great Martian storms of 1909, 1911, and 1924 noting after the last one, that the planet had become covered with yellow clouds and presented a color similar to Jupiter.

On Mercury his observations made between 1914 and 1929 seemed to confirm Giovanni Schiaparelli's rotation period of 88 days, identical with the planet's period of revolution around the Sun. The effect of this would be for Mercury always to turn the same face to the Sun, in the same way as the Moon always turns the same face to the Earth. Antoniadi cited nearly 300 observations of identifiable features always in the same position, as required by the 88-day rotation period.

However radar studies of Mercury in 1965 revealed a 59-day rotation period for Mercury. This time is however very close to half the synodic period of Mercury (116 days) so that when the planet returns to the same favorable viewing position in the sky, at intervals of 116 days, it does present the same face to observers.

Antoniadi also wrote on the history of astronomy, publishing L'Astronomie Égyptienne in 1934.