Karzai was the son of the chief of the Popalzai Pashtuns, and both his father and grandfather served in the government of Mohammad Zahir Shah (Zahir Shah, Mohammad). Under the Soviet-imposed regime in the 1980s, the Karzai family left Afghanistan and settled in Pakistan. Karzai attended Himachal Pradesh University in India, earning a master's degree (1982) in political science. During the Afghan War, he worked with the mujahideen, who sought to overthrow the Soviet-backed government, and often traveled to the United States to seek support for the cause. When the communist government of Mohammad Najibullah (Najibullah, Mohammad) fell in April 1992, the mujahideen established a coalition government, with Karzai serving as deputy foreign minister. In 1994, however, he resigned, tired of the infighting within the government. The growing strife escalated until the mujahideen turned on one another, and in the ensuing turmoil, the Taliban, an ultraconservative political and religious faction, came to power.

Although initially supportive of the Taliban and the order that it introduced to the country, Karzai came to oppose the regime and again went into exile in Pakistan. In July 1999 his father was assassinated, an act that he blamed on the Taliban, and leadership of the Popalzai passed to Karzai. Shortly after the September 11 attacks in 2001, the United States led a military campaign to topple the Taliban and to capture terrorists that were based in the country. Karzai returned to Afghanistan to rally support for the U.S.-led mission, and by mid-November the Taliban regime had collapsed. To avert a destructive power struggle, representatives from various Afghan groups, aided by the international community, named Karzai chair of an interim administration; he was sworn into office in late December 2001. In June 2002 a Loya Jirga, a traditional Afghan assembly, chose Karzai as president of a transitional government.

Karzai faced numerous challenges, including controlling the country's powerful traditional leaders and preventing the Taliban from recovering power. He also sought to rebuild the war-torn country. Violence continued to plague Afghanistan, and Karzai was the target of several assassination attempts. In January 2004 a new constitution was approved that called for a directly elected president. Later that year Karzai won the presidential election and was sworn into office.