The institute took its current form in March 2012, when two arms of the National Observatory of Athens merged: the Institute of Astronomy and Astrophysics, and the Institute for Space Applications and Remote Sensing. But the roots run far deeper. The astronomy side descends from an Astronomical Institute founded in 1890, which in turn carried on a tradition that began with the building of the Observatory of Athens in 1842, the first scientific research institution in the modern Greek state. The space-sensing side started as the Ionospheric Institute in 1955. Today the whole operation works from the Penteli Observatory campus on Mount Penteli, about 16 km from the historic observatory that still stands in central Athens, facing the Parthenon across the city.

For the deepest observations, astronomers climb far from the city lights. On the Helmos mountain chain in the northwestern Peloponnese, 2,340 meters above sea level under some of the darkest skies in the country, sits the Aristarchos telescope. Its 2.3-meter mirror, built by Carl Zeiss in Germany, is the largest in Greece. Paired with sensitive detectors and the clear mountain air, it can study objects in our own Galaxy and trace the faintest, most distant points of light at the outskirts of the universe. Its instruments include a camera, a fiber-fed spectrograph, and a tool dedicated to catching the tiny dimming of stars as exoplanets cross in front of them.

Some of the institute's instruments are monuments in their own right. The Newall refractor, a 62.5-centimeter telescope, was commissioned by Robert Stirling Newall, a wealthy Scottish engineer and amateur astronomer, for his private observatory near Gateshead. Built by Thomas Cooke, it was donated to the University of Cambridge in 1890, then given to Athens in 1957, and since 1995 it has served as the institute's main public outreach telescope. The Doridis telescope, built in 1902 and funded by the benefactor Dimitrios Doridis, remained the largest in Greece for fifty-seven years; restored in 2014, it now shows planets, comets, and the moon to visitors. The Kryoneri station on Mount Kyllini, established in 1972, has been upgraded to hunt for meteor flashes on the moon.

The institute's gaze also turns downward and outward at once. A magnetometer array called ENIGMA tracks disturbances in Earth's magnetic field for space-weather research, part of the global SuperMAG network. An ionospheric sounder at Penteli, running around the clock since 2000, probes the charged upper atmosphere and feeds data to international networks and the European Space Agency. On a rooftop near the city center, an atmospheric station has measured Athens' air and sunlight since 2009 as part of NASA's AERONET network, classifying Saharan dust, smoke, and volcanic ash drifting over the city. Satellite dishes pull in streams from missions like NASA's Aqua and Terra and Europe's Copernicus Sentinels, turning raw downlinks into alerts for dust, fire, and earthquakes.