Khalilzad’s wife is author and political analyst Cheryl Benard. They met in 1972 while they were both students at the American University of Beirut. They have two children: Alexander and Maximilian.

From 1979 to 1989, Khalilzad worked as an Assistant Professor of Political Science at Columbia University’s School of International and Public Affairs. During that time, he worked closely with Zbigniew Brzezinski, the Carter administration’s architect of Operation Cyclone to support the mujahideen, who resisted the Soviet Union’s invasion of Afghanistan.

In 1984, Khalilzad accepted a one-year Council on Foreign Relations fellowship to join the US State Department, where he was an adviser to the Near East and South Asia Bureau, headed by Richard W. Murphy.

From 1985 to 1989, Khalilzad served in the Reagan administration, as a senior State Department official, advising on the Soviet–Afghan War, after the Soviet invasion. During that time, he was a member of the Policy Planning Staff and the State Department’s Special Adviser on Afghanistan to Undersecretary of State Michael H. Armacost. In that role, he developed and guided the international program to promote the merits of a mujahideen-led Afghanistan ousting the Soviet occupation. From 1990 to 1992, Khalilzad served under President George H. W. Bush in the US Defense Department, as Deputy Undersecretary for Policy Planning.

Between 1993 and 2000, Khalilzad was the director of the Strategy, Doctrine, and Force Structure at the RAND Corporation. During that time, he helped found RAND’s Center for Middle Eastern Studies as well as “Strategic Appraisal,” a RAND periodical. He also authored several influential monographs, including “The United States and a Rising China” and “From Containment to Global Leadership? America and the World After the Cold War.” At RAND, he also had a brief stint in consulting for Cambridge Energy Research Associates, which was conducting a risk analysis for Unocal, now part of Chevron, for a proposed 1400 km (890 mi), $2-billion, 622 m³/s (22,000 ft³/s) Trans-Afghanistan gas pipeline project, which would have extended from Turkmenistan to Afghanistan and then proceeded to Pakistan.

Khalilzad also wrote several articles on the subject of the value of U.S. global leadership in the mid-1990s. The specific scenarios for conflict that he envisioned if a decline in American power occurred have made his writings extremely popular in competitive high school and college policy debate, particularly his writing that links the loss of US hegemony to global instability. Khalilzad was a signatory of the letter from members of the Project for the New American Century to President Bill Clinton sent on January 26, 1998. It called for Clinton’s help in “removing Saddam Hussein and his regime from power” by using “a full complement of diplomatic, political and military efforts.”

In 2001, President George W. Bush asked Khalilzad to head the Bush-Cheney transition team for the Department of Defense, and Khalilzad briefly served as Counselor to Secretary of Defense Donald Rumsfeld. In May 2001, National Security Adviser Condoleezza Rice announced Khalilzad’s appointment as Special Assistant to the President and Senior Director for Southwest Asia, Near East, and North African Affairs at the US National Security Council. In December 2002, Bush appointed Khalilzad to the position of Ambassador at Large for Free Iraqis with the task of coordinating “preparations for a post-Saddam Hussein Iraq.”

After the terrorist attacks of 9/11, Bush came to rely on Khalilzad’s Afghanistan expertise. Khalilzad was involved in the early stages of planning to overthrow the Taliban and on December 31, 2001, he was selected as Bush’s Special Presidential Envoy for Afghanistan. He served in that position until November 2003, when he was appointed to serve as US ambassador to Afghanistan. Khalilzad held that position from November 2003 until June 2005.

During that time, he oversaw the drafting of the constitution of Afghanistan, was involved with the country’s first elections and helped to organize the first meeting of Afghanistan’s Loya Jirga(traditional grand assembly). At the June 2002 Loya Jirga to select the Head of State, representatives of the US convinced the former king of Afghanistan, 87-year-old Zahir Shah, to withdraw from consideration even though a majority of Loya Jirga delegates supported him. That move angered Pashtuns, who were concerned with the disproportionate power of the Northern Alliance in the Karzai government. During Khalilzad’s tenure as ambassador, the new Afghan president, Hamid Karzai, consulted closely with him on a regular basis about political decisions, and the two dined together regularly. In 2004 and 2005, he was also involved in helping with the establishment of the American University of Afghanistan (AUAF), which is the first American-style higher learning educational institution in Afghanistan. In 2016, the Friends of the American University of Afghanistan presented him with the International Public Service Award.

Khalilzad began his job as US Ambassador to Iraq on June 21, 2005. He was credited for helping negotiate compromises which allowed the ratification of the Constitution of Iraq in October 2005. Khalilzad also worked to ensure that the December 2005 elections ran smoothly and played a substantial role in forming the first post-Saddam government. Khalilzad also helped establish the American University of Iraq, in Sulaimaniya, and sits on its board of regents.

Khalilzad was one of the first high-level administration officials to warn that sectarian violence was overtaking the insurgency as the top threat to Iraq’s stability. After the Al Askari Mosque bombing, in February 2006, he warned that spreading sectarian violence might lead to civil war and possibly to even a broader conflict, involving neighboring countries. Khalilzad sought political solutions to the problem of sectarianism, and in particular, he worked to integrate the balance of power between Iraq’s three main ethnic groups to head off growing the growing Sunni violence.

Khalilzad’s term as ambassador ended on March 26, 2007. He was replaced by Ryan Crocker, a career diplomat and former US ambassador to Pakistan.

On February 12, 2007, the White House submitted Khalilzad’s nomination to the Senate to become the US ambassador to the United Nations. He was unanimously confirmed by the Democratic-controlled US Senate on March 29, 2007. That marked a strong contrast to Khalilzad’s predecessor, John R. Bolton, whose often-controversial rhetoric caused him to fail to be confirmed by the Senate but obtained a recess appointment.

In November 2007, Khalilzad charged that Iran was helping the insurgent groups in Afghanistan and Iraq. He also told the media, soon after the International Atomic Energy Agency’s release of its report on Iran, that the Iranian government was clearly going ahead with its nuclear program. Khalilzad explained that the US would try to pass another resolution in the Security Council, under Chapter 7, to impose additional sanctions against Iran.

In August 2008, he urged the Security Council to “take urgent action” and to “condemn Russia’s military assault on the sovereign state of Georgia”. He also stated that Russian Foreign Minister Sergey Lavrov had told US Secretary of State Rice that Georgian President Mikheil Saakashvili “must go.”

From 2009 to 2018, Khalilzad served as the President of Khalilzad Associates, LLC, an “international advisory firm that serves clients at the nexus of commerce and public policies, helping global businesses navigate the most promising and challenging international markets.” Khalilzad Associates and its parent company, Gryphon Capital Partners, have, as clients, international and US companies that interested mainly in doing business in Iraq and Afghanistan. According to Khalilzad, they include companies in the sectors of energy, construction, education, and infrastructure.

On September 9, 2014, a news items appeared in the Austrian media, stating that Khalilzad was being investigated by authorities in Austria for suspected money laundering, and that his wife’s accounts had been frozen. On September 10, the Austrian court made known that the case had been dismissed and the accounts had been ordered unfrozen a week earlier, on September 3. The leak was the result of court documents having been discarded unshredded in the general trash, and then found by scavenging bloggers.

In 2015, he donated over $100,000 to the Atlantic Council, a US thinktank.

Khalilzad’s political autobiography, The Envoy: From Kabul to the White House, My Journey Through a Turbulent World, was published by St. Martin’s Press in 2016.

Khalilzad, like most US politicians, supported Kosovo’s declaration of independence. In 2017, he was awarded the Order of Independence medal from Kosovo President Hashim Thaçi.

In September 2018, Secretary of State Mike Pompeo named Khalilzad as the Special Representative for Afghanistan Reconciliation, a newly created envoy with the mission of securing a peaceful resolution to the conflict in Afghanistan.