The blast occurred shortly after 7:30 a.m. local time at a two-story building on Lysicratous Street in Athens' historic Plaka district near the Acropolis.
The six bodies are believed to be those of four US nationals staying in a first-floor short-term rental and an elderly Greek woman and her British husband who lived on the second floor, according to ERT.
The explosion also injured two women in a nearby building and a passerby. All three were rescued and taken to hospital, Xinhua reported.
The cause of the explosion remains under investigation. Authorities are examining a possible fault in the natural gas network in the building or a neighboring property, following reports that residents smelled gas before the blast.