President John Kufuor is stepping down after serving the maximum two terms and the race to succeed him is a tight one.
Nana Akufo-Addo, who served as foreign minister under Mr Kufuor, is the New Patriotic Party’s contender.
John Atta Mills of the opposition National Democratic Congress is standing for office for a third time.
As Ghana’s electoral commission is widely seen as independent, the country’s destiny should now be in the hands of the voters, says the BBC’s Will Ross in the capital, Accra.
Most will put a thumb print next to a candidate from one of two main parties.
Nana Akufo-Addo, a British-trained lawyer, is promising an industrial revolution in Ghana.
John Atta Mills has served as vice-president under Ghana’s former leader Jerry Rawlings.
There is little love lost between the two main political parties, our correspondent says, and both are confident of victory.
The Convention People’s Party, which ushered in Ghana’s independence, has picked up support from people disillusioned with the two main parties.
Its candidate, Paa Kwesi Nduom, may secure enough votes to prevent the other leading candidates from achieving a first-round victory, says our correspondent.
This election is important not just for Ghana, but also for the continent, he says.
Emmanuel Bombande, who works for the West Africa Network for Peace Building, said: “I have been travelling of late in many African countries and what people keep on saying is ‘Ghana, please redeem our image, be the good example. Don’t go the way Kenya went or Zimbabwe has gone and we count on you to do that’.
“And I can see people are looking at Ghana for leadership when it comes to governance and democracy.”
The fact that the hallmark for a successful election is that it is peaceful is seen by some as a worrying sign of just how low the bar has been set when it comes to judging democracy in Africa, says our correspondent.