Record early voting indicates turnout will be high after a campaign dominated by mud-slinging between liberal Lee Jae-myung and conservative Yoon Suk-yeol.
The pair have been neck-and-neck in the polls for months, with around 90 percent of the electorate supporting one or the other.
Analysts say South Korean politics is particularly adversarial, with democracy only restored in 1987 after decades of authoritarian rule.
Presidents serve just a single term of five years, and every living former leader has been jailed for corruption after leaving office.
Yoon has already threatened to investigate outgoing President Moon Jae-in, citing unspecified "irregularities".
Polling stations open at 6 am (2100 GMT) and shut at 6 pm. For 90 minutes after closing, Covid-positive voters will be allowed to cast their ballots.
South Korea is in the grip of an Omicron wave with more than 200,000 new cases being recorded on most days this month.
More than a million people are currently isolating at home after testing positive, health authorities say. The country amended its electoral laws last month to ensure they would be able to vote.
In a two-day early voting exercise last week, a record-breaking 37 percent of the 44 million people eligible cast their ballots -- the highest number since the system was introduced in 2013.
Polls show the top concerns among the electorate are skyrocketing house prices in the capital Seoul, rising domestic inequality and stubborn youth unemployment.
The new president will also have to confront an increasingly assertive North Korea, which has embarked on a record-breaking blitz of weapons tests this year including a launch just days before the election.
'Tone deaf'
Lee, a former child factory worker turned politician, has offered a slew of fresh policies from a universal basic income to free school uniforms -- but his ideas have been overshadowed by media coverage of scandals.
The 57-year-old is under pressure over a controversial land development deal in which private investors profited from a state-funded project on Lee's watch as mayor of the city of Seongnam.
He was also forced to start his campaign by apologising for a profanity-laden phone call with his family involving disputes with his late brother and mother.
His conservative rival Yoon has called for a relaxation of labour regulations including a lowering of the minimum wage and the removal of limits on working hours.
The former top prosecutor is also promising to abolish the gender equality ministry, saying South Korean women do not suffer from "systemic gender discrimination", despite evidence to the contrary.
Yoon has made a series of gaffes on the campaign trail including most recently with a tweet on Ukraine in which he posted a tangerine with an angry face in a bizarre reference to the country's Orange Revolution of 2004.
Critics described the tweet as "tone deaf".
The winner of the election will formally succeed Moon in May. The incumbent remains popular, despite not achieving a promised peace deal with North Korea.
