The Islamists have rejected the election as a foreign plot, and urged their fighters to attack polling staff, voters and security forces.
Afghanistan's third presidential election brings an end to 13 years of rule by Karzai, who has led the country since the Taliban were ousted in a US-led invasion in 2001.
The NATO coalition force is pulling out its last 51,000 combat troops this year, leaving Afghan forces to battle the resilient Taliban insurgency without their help.
Poll security is a major concern following a string of high-profile attacks in the capital Kabul, most recently a suicide bombing at the Interior Ministry on Wednesday that killed six police officers.
Interior Minister Omar Daudzai said all 400,000 of Afghanistan's police, army and intelligence services were being deployed to ensure security around the country.
While there have been no significant attacks on the candidates, a charity's guesthouse, a luxury hotel and offices of the Independent Election Commission have all been hit.
The eve of the poll was overshadowed by the killing of award-winning Associated Press photographer Anja Niedringhaus, shot by a police commander in eastern Afghanistan.
Niedringhaus, 48, was the third journalist working for international media to be killed in Afghanistan during the election campaign, after Swedish journalist Nils Horner and Sardar Ahmad of Agence France-Presse.
Horner was shot dead in the street in Kabul, while Ahmad was killed along with his wife and two of his three children in a Taliban attack on the city's Serena Hotel.
- No clear favourite -
Polls open at 7:00 am (0230 GMT) and close at 4:00 pm, with around 13.5 million people eligible to vote from an estimated total population of 28 million.
As well as the first round of the presidential election, voters will also cast ballots for provincial councils.
The front-runners to succeed Karzai, who is constitutionally barred from standing again, are former foreign minister Zalmai Rassoul, Abdullah Abdullah -- runner up in the 2009 election -- and former academic Ashraf Ghani.
There is no clear favourite and if no candidate wins more than 50 percent of the vote in the first round -- preliminary results for which will be announced on April 24 -- a run-off is scheduled for late May.
Massive fraud and widespread violence marred Karzai's re-election in 2009 and a disputed result this time would add to the challenges facing the new president.
Whoever emerges victorious must lead the fight against the Taliban without the help of more NATO troops, and also strengthen an economy reliant on declining aid money.
The election may offer a chance for Afghanistan to improve relations with the United States, its principal donor, after the mercurial Karzai years.
Ties fell to a new low late last year when Karzai refused to sign a security agreement that would allow the US to keep around 10,000 troops in Afghanistan to train local forces and hunt Al-Qaeda.