His main challenge is expected to come from ex-military leader Muhammadu Buhari, who has strong support in the mainly Muslim north of the country.
Mr Jonathan is counting on opposition divisions to win outright, avoiding a run-off election.
Polling stations open at 0800 (0700 GMT) but voting only starts after noon.
Everyone intending to vote is required to register for accreditation before midday.
The sitting president has staked his reputation on the conduct of the election, repeatedly promising it will be free and fair.
Africa's largest oil producer has long been plagued by corruption and has a history of vote fraud and violence.
The head of the African Union's observer mission, former Ghanaian President John Kufuor, said some shortcomings had been found with the election process but he was confident the electoral commission would resolve them.
'Model for Africa'
Nigerians are pinning their hopes on this being their cleanest election in decades.
Mr Jonathan is the first head of state from the southern, oil-producing Niger Delta.
In addition to Mr Buhari, he is facing a challenge from former anti-corruption chief Nuhu Ribadu and Kano state governor Ibrahim Shekarau, though both are seen as rank outsiders.
While his People's Democratic Party lost seats in a parliamentary election last week, Mr Jonathan has enjoyed a lead in opinion polls.
The fact that talks between Nigeria's two main opposition parties - fielding Mr Buhari and Mr Ribadu - to agree a formal alliance for the presidential poll broke down has played in his favour.
Mr Buhari will need to prevent him from taking at least a quarter of the votes in two thirds of the country's 36 states if he is to stop him winning in the first round, a feat which northern support alone is unlikely to guarantee, Reuters news agency notes.
The relatively successful conduct of the parliamentary election has increased confidence in the ability of the electoral commission, Inec, to ensure a fair presidential vote.
However, bomb blasts and other attacks have killed dozens in the run-up to the polls.
With 73 million registered voters, Nigeria has the biggest electorate on the continent.
"If Nigeria gets it right, it will impact positively on the rest of the continent and show the rest of the world that Africa is capable of managing its electoral processes," said Mr Kufuor.
"If Nigeria gets it wrong, it will have a negative influence on the continent with dire consequences."