The explosion on Friday occurred in an old two-storey building in the Plaka district, the historic part of Athens that lies at the foot of the Acropolis hill, Greece's most visited ancient monument.
The building collapsed, while neighbouring buildings were also damaged.
Firefighters rescued two women from an adjacent building, with police saying both were being transported to a hospital.
Local media said a passer-by was also slightly injured by the blast.
Police cordoned off the area, while rescuers with a sniffer dog were deployed to check whether any more people might be trapped.
Local media reported that up to five people might have been inside the building at the time of the blast, but there was no confirmation.
The fire department said the search and rescue operation was still ongoing several hours after the explosion.
The pastor for a nearby church said this Sunday's service would be held outdoors due to damage to the church from the explosion.
"Of course we went in. It was heartbreaking. From the bottom to the top, there is no window that has not been broken," said Giotis Kantartzis, pastor of the First Greek Evangelical Church in Athens.
Video from the scene showed rubble strewn across the street, with parked cars smashed by falling debris.
The cause of the explosion was not immediately clear, but local media said a gas leak was suspected.
