Polling stations opened at 07:00 local time (04:00 GMT) and will close 12 hours later, although officials said voting could be extended for five hours if there is a big turnout.
President Bashar al-Assad is seeking a third term in office. He will face Maher Abdel Hafiz Hajjar, a lawmaker from Aleppo, as well as Hassan Abdallah al-Nuri, a legislator from Damascus in the forthcoming presidential race.
President Assad is widely expected to win a third seven-year term in office.
The poll takes place three years into a civil war in which tens of thousands of people have died and millions more are displaced.
It is the first time in decades that more than one name has appeared on the ballot paper.
Previous presidential terms have been called through a referendum with just one member of the Assad family on the ballot paper.
Campaigning officially ended on Monday and workers across central Damascus removed banners, posters and pictures of the candidates.
Prime Minister Wael al-Halqi said the election was a "historic day" for Syria and that a large turnout would "prove to the entire world that the Syrian people have decided and are determined to make the electoral process a success".
He urged Syrians to elect a president who would "achieve security and stability in the country... and step up the achievement of national reconciliation".
The interior ministry says there are 15.8 million eligible voters, both inside and outside Syria, and about 9,600 polling stations have been set up around the country.
However, voting will only take place in government-held territory, with several parts of the country either under rebel control or in areas being fought over.
Militant groups have warned they will try to disrupt the vote and the so-called Syrian National Coalition is boycotting it.
Government forces have recently made significant military victories while some militant groups have been fighting among themselves.
On May 28, Syrian citizens living abroad went to the polls at the Syrian embassies in a number of countries including Iran, Russia, Yemen, China, Lebanon, Malaysia, Venezuela, Jordan, Sudan, Oman, the Czech Republic, Belarus and India.
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