The Afghan leader along with other high-ranking officials arrived at Amani High School at around 7.35 a.m. to cast his vote, Xinhua reported.
Among the officials accompanying Karzai were First Vice President Mohammad Younus Qanooni, Defence Minister General Bismillah Mohammadi and other cabinet ministers.
Karzai, who is constitutionally barred from running for a third consecutive five-year term, urged all Afghan voters to take part in the election process.
Afghans began voting on Saturday morning to elect a new president for the next five years in the country's first democratic transfer of power through polling.
The polling will close at 4 p.m.