Although few deaths were reported in the early violence, more casualties were expected as the Afghan government lifted its media blackout on the reporting of violence.
About 17 million Afghans were eligible to vote.
Karzai, who cast his vote at a polling station near the presidential palace in Kabul early in the day, faces challenge mainly from former foreign minister Abdullah Abdullah, former finance minister Ashraf Ghani and former planning minister Ramazan Bashardost. All three had once served in Karzai's government.
Voters were electing not only a president but also 420 provincial council members for the country's 34 provinces.
Thousands of observers including hundreds of foreign observers were overseeing the balloting at more than 6,500 polling centres while the commission said it was unable to open voting stations in nine districts that remain outside government control.
Although Karzai led in recent opinion polls, he was not expected to receive more than 50 percent of the vote to win the election outright. If no candidate posts a first-round majority, a run-off would be held in the first week of October.