Karzai was born in Kandahar, Afghanistan. An ethnic Pashtun and a member of the powerful Populzai clan (from which many Afghan Kings have come), he came from a family that were among the strongest supporters of King Zahir Shah. Thus, he became involved in political landscape in Afghanistan early on. He took a postgraduate course in political science at Himachal University in Shimla, Himachal Pradesh, India from 1979 to 1983, then returned to financially support anti-Soviet uprisings in Afghanistan during the rest of the 1980s. After the expulsion of Soviet forces, he served as a minister in the government of Burhanuddin Rabbani.
When the Taliban emerged onto the political scene in the 1990s, Karzai was initially among their supporters. However, he later broke with the Taliban, citing distrust of their links to Pakistan. After the Taliban overthrew Rabbani in 1996, Karzai refused to serve as their U.N ambassador. In 1997 Karzai joined many of his family members in Quetta, from where he worked to reinstate Zahir Shah.
In 2001, following the September 11 terrorist attack, Karzai worked with agents of the United States to overthrow the Taliban in Afghanistan and muster support for a new government. On December 5, 2001, he was named leader of an interim government.
On September 5, 2002, an assassination attempt was made on Hamid Karzai in Kandahar. A gunman wearing the uniform of the new Afghan National Army opened fire, wounding the Governor of Kandahar and an American Special Operations officer. The gunman and one of the President's bodyguards were killed.
His brother Ahmed Wali Karzai helps coordinate humanitarian assistance in the southern province of Kandahar.