Official results with just more than 40% of the total vote in the Greek election today counted showed Karamanlis' New Democracy party ahead with 43.7% and the opposition socialist PASOK party in second place with 38.5%.
Initial official figures showed turnout at 70%.
Several other polling agencies conducting exit polls for private TV stations all showed similar results, projecting that New Democracy was ahead with between 40.2% and 43.7%, and PASOK was in second place with between 36.5% and 39.8%.
They also said surveys indicated the right-wing nationalist LAOS party had won enough votes to enter parliament.
If confirmed, the projections would indicate a slip in support for both parties from the previous election in 2004, when New Democracy had won with 45.4%, ahead of PASOK with 40.5%.
"The government won under very difficult circumstances. Of course there is a message for New Democracy which we must listen to," said Athens Mayor Nikitas Kaklamanis, a senior official in New Democracy.
It was likely - but not certain - that New Democracy would win enough seats in the 300-member unicameral parliament to form a governing majority by itself. Should it do so, it would be only the party's second re-election in its 33-year history.
Before the election, Karamanlis had ruled out forming a coalition with any other party if he did not win enough votes to form a majority government and the election resulted in a hung parliament.
"I think it will be a long night to see if we get a governing majority," said Yiannis Vlastaris, managing editor of the left-leaning Sunday Eleftherotypia newspaper. "It was certainly a good night for the left-wing opposition parties. A slim majority does not necessarily mean a weak government."
PASOK party veteran Kimon Koulouris agreed the final result was still not clear.
"It will be a long night. … The question of a hung parliament remains open," he said.
Outgoing Health Minister Dimitris Avramopoulos was more confident.
"It appears New Democracy will form a governing majority," he said. "The size of the majority will not affect how effective our government is. Even with 151 deputies in parliament, we will proceed with our reform program."
RASS-MARC showed LAOS winning a projected 3.5% - half a percentage point more than the minimum required for a seat in the legislature.
The other two parties that were projected to remain in parliament are both left-wing - the KKE communist party and the SYRIZA left-wing coalition. The exit polls predicted KKE would win between 6.4 and 9%, and SYRIZA would get between 4.5 and 6%.
"I thank the Greek voters who allowed the presence of a fifth party in parliament," said LAOS candidate Pangiotis Theodorakidis. "We just hope the exit poll results are the same as the official returns."
Karamanlis had appeared certain of re-election when he called in mid-August for early polls. But his chances were threatened by the fires that broke out a week later, leaving his government reeling from criticism of a slow and disorganized response to the disaster.
He was also challenged by the emerging LAOS party. LAOS ran on a platform including immigration quotas and opposition to Turkey's bid to join the European Union, but analysts had said it was likely to win protest votes from conservatives upset with New Democracy but unwilling to vote for a left-wing party.
Some 9.8 million Greeks were eligible to vote, out of an estimated population of 11.2 million, casting ballots at 20,509 polling stations in 56 electoral districts.