Police cordoned off the area where an unknown attacker fired an automatic rifle at the building on the capital's busy Syngrou Avenue, south of the city centre.
No group claimed responsibility for the attack, which occurred amid a renewed wave of politically motivated violence by small anarchist and far-left groups.
Government spokesman Simos Kedikoglou said a bullet hit the window of the office used occasionally by Prime Minister Antonis Samaras and was found inside the room. No party officials were in the building at the time. The official prime minister's office is at another building in central Athens, where he spends most of his time.
"Of course there could have been (victims). There could have been a cleaner in the prime minister's office or a security guard at the site," Kedikoglou said.
Police said the attacker was believed to have had at least one accomplice, while experts were examining a car found abandoned and burned near the scene.
The conservative New Democracy heads a three-party coalition government formed after elections in June and is leading Greece's painful economic recovery effort to cut its high public debt and budget deficit through deeply resented spending cuts and tax hikes.
Over the weekend, arsonists attacked the home of the brother of government spokesman Kedikoglou with a firebomb.
The unknown attackers broke down the door with a sledgehammer and threw a firebomb inside. No one was hurt.