"I urge the Afghan nation to go to the polling stations despite the rain, cold weather and enemy threats ... and to take the country another step towards success," Karzai, who cannot stand again himself, said after voting at 8.00am in a Kabul school.
Security, fraud and abstention were the main obstacles to a successful poll but enthusiasm for the vote seemed to be high on Satuday morning.
The Taliban has threatened to disrupt the election and has launched attacks, including one on the Indepedent Election Commission, ahead of the vote.
Ten per cent of polling stations were closed because they were deemed unsafe, correspondent Maeva Bambuck told RFI, and all of Afghanistan's 400,000 police, army and intelligence services were deployed.
A bomb wounded two peole at a polling station in a school in Logar province, south of Kabul, provincial spokesperson Din Mohammad Darwish told the AFP news agency.
"They don't want the political process to succeed and they want to hurt the credibility of the elections," one of the leading candidates, Abdullah Abdullah, told the media ahead of polling day.
Foreign journalists have also been attacked - Associated Press photographer Anja Niedringhaus was killed and AP reporter Kathy Gannon wounded by an Afghan policeman in the eastern city of Khost on Friday and Swedish-British journalist Nils Horner was shot dead in Kabul in March.
Eight candidates were still standing by polling day and about 13.5 million people were eligible to vote.
The election marks the end of Karzai's 13 years in power, following his naming as president after the toppling of the Taliban government, and will be the first peaceful passage of power following a vote.
If no clear winner emerges from Saturday's vote it will go to a second round on 28 May.
The next president will face the challenge of running a poor and unstable country as foreign combat troops pull out in 2015.