The first national archaeological museum of Greece was established in 1829 by Ioannis Kapodistrias, the first head of state of newly independent Greece, and it lived at first on the island of Aegina, which was then the capital. As the capital moved to Athens, the collection moved with it, shuttled through several temporary buildings until 1858, when an international architectural competition was announced. The current site on Patission Street was chosen, construction began in 1866, and the building was completed in 1889 with funds from the Greek government, the Greek Archaeological Society, and private donors. Eleni Tositsa donated the land. Demetrios and Nikolaos Vernardakis, brothers who had made fortunes in Saint Petersburg, paid for completing the structure. Originally called the Central Museum, it was renamed in 1881 by Prime Minister Charilaos Trikoupis to the name it bears today. The neoclassical building, designed by Ludwig Lange and modified by Panagis Kalkos, Armodios Vlachos, and Ernst Ziller, sits in deliberate visual harmony with the artifacts it houses.

When German forces invaded Greece in April 1941 and Athens fell within weeks, the museum's curators did something extraordinary. They closed the museum, packed every major antiquity into custom protective boxes, and buried them. The largest sculptures were lowered into trenches dug in the museum's basements and sealed. Smaller objects went into vaults. For four years the most important collection of Greek antiquity in the world lay underground, in darkness, while the city above it starved. Christos Karouzos and his wife Semni Karouzou ran the burial program and survived the occupation. In 1945, with the Germans gone, they reopened the museum and brought the antiquities back into the light. The Karouzoi published catalog after catalog through the 1950s and 1960s, walking generations of visitors through what they had saved.

The prehistoric collection alone could fill a major museum. Neolithic figurines from Dimini and Sesclo. Cycladic marble sculptures from the third millennium BC, simplified almost to abstraction, that inspired Henry Moore and Constantin Brancusi when European modernists rediscovered them in the early twentieth century. The harpist from Keros, sitting cross-legged with his lyre, is one of the earliest images of a musician in Western art. The Mycenaean rooms hold Schliemann's gold from Grave Circle A, including the Mask of Agamemnon, plus the two Vapheio cups beaten from sheet gold and showing scenes of bull-capture in such detail that you can see the texture of the rope. Linear B tablets in adjacent cases preserve the bookkeeping of palaces that burned around 1200 BC. Then come the great kouroi, the Archaic statues of young men: the Sounion Kouros, eight feet tall and severe; the Phrasikleia Kore, a young woman with her name in stone explaining she will be called maiden forever because the gods denied her marriage.

On October 8, 1900, a sponge diver off the small island of Antikythera came up from a wreck in 60 meters of water with a story about a heap of bronze statues and a corroded mass of geared metal. The Greek government chartered a salvage operation that recovered the wreck of a Roman-era ship that had gone down around 65 BC carrying a cargo of looted Greek art. Among the bronzes was a youth, the Antikythera Ephebe, his weight on one foot, his missing hand once holding something the experts still argue about. Among the corroded geared masses was the Antikythera Mechanism, which X-ray tomography in the 21st century revealed to be an astronomical calculator with at least thirty interlocking bronze gears, capable of predicting eclipses and tracking the cycles of the moon and the planets. Both are in the museum now, in adjacent rooms. They are objects from the same ship, made within a generation of each other, and together they argue that the Hellenistic world was both more artistically refined and more technologically advanced than later ages assumed possible. The library next door holds twenty thousand volumes, including the original excavation diaries of Heinrich Schliemann, and is named for Alexander Onassis.