The poll is seen as a crucial step to restoring peace in the country gripped by sectarian violence.
Officials are counting ballots in French in the Central African Republic capital, Bangui.
General Balla Keita, from the United Nations force operating in the country, says, so far, there has been little trouble.
"So all the polling stations except one or two, you know, have started a little bit late. Now people have started the voting, and everything is calm. The situation is under control, and so they look, you know, pretty happy."
Officials said about 80 per cent of the eligible population turned out to vote in the first round of elections in December.
Now, two former prime ministers, Faustin Touadera and Anicet Dologuele, are contesting the presidential run-off.
Both are Christians.
The first round was widely seen as a rejection of the violence that has left the north-east of the country under the control of Muslim rebels while Christian militias roam the south-west.
But speaking to Al Jazeera, this Bangui resident says he feels the elections have been rushed.
"This election has been badly prepared. There hasn't been enough time. The international community has pushed us towards these elections. We have said they should happen but they must be good elections so we don't have people contesting the result afterwards. "
Voters have also been choosing a new parliament.
Many in the Central African Republic are hoping the vote will bring lasting peace.
The country was plunged into the worst crisis in its history in early 2013 when mainly Muslim Seleka fighters toppled President Francois Bozize.
More than two years of sectarian fighting have left thousands of people dead.
Nearly one million people have been forced from their homes, about half of them now in neighbouring Cameroon, Chad and Congo.
Lewis Mudge, from the rights group Human Rights Watch, says the continuing insecurity is concerning.
"What really needs to happen is there needs to be a base level of security. People need to have the security and the confidence to start to regain their lives. And most people that I'm speaking to know that's not going to come simply with an election. The elections are not going to be the silver bullet* that everyone wants them to be."
The final results of the run-off are not expected for several weeks.