Her family left Lebanon when she was two years old, during the Lebanese Civil War, and settled in Gerrards Cross, Buckinghamshire. Her father, Ramzi Alamuddin, a Lebanese Druze from the Alamuddin family of Baakline (a village in the Chouf district), received his MBA degree at the American University of Beirut. He returned to Lebanon in 1991. Her mother, Bariaa (née Miknass), from a family of Sunni Muslims from Tripoli in Northern Lebanon, is a political journalist and foreign editor of the Pan-Arab newspaper al-Hayat and a founder of the public relations company International Communication Experts, which is part of a larger company that specialises in celebrity guest bookings, publicity photography, and event promotion.

Alamuddin attended Dr Challoner’s High School, a girls’ grammar school located in Little Chalfont, Buckinghamshire. She then studied at St Hugh’s College, Oxford, where she received an Exhibition and the Shrigley Award. In 2000, Clooney graduated with a BA degree in Jurisprudence.

The following year, in 2001, she entered New York University School of Law to study for the LLM degree. She received the Jack J. Katz Memorial Award for excellence in entertainment law. For one semester while at NYU, she worked in the office of Sonia Sotomayor, then a judge for the United States Court of Appeals for the Second Circuit.

Alamuddin is qualified to practise as a lawyer in the United States and the United Kingdom. She was admitted to the bar in New York in 2002, and in England and Wales in 2010. She has also practised at international courts in The Hague including the International Court of Justice and the International Criminal Court.

In 2004, she completed a judicial clerkship at the International Court of Justice. She clerked under Judge Vladlen S. Vereshchetin from Russia, Judge Nabil Elaraby from Egypt, and ad hoc Judge Sir Franklin Berman from the United Kingdom.

Alamuddin returned to Britain in 2010, where she became a barrister in London (Bar of England & Wales, Inner Temple) at Doughty Street Chambers. In 2013 she was appointed to a number of United Nations commissions, including as adviser to Special Envoy Kofi Annan on Syria and as Counsel to the 2013 Drone Inquiry by UN human rights rapporteur Ben Emmerson QC into the use of drones in counter-terrorism operations.

As of 2011, Alamuddin was assisting the Permanent Court of Arbitration in the arbitration between Merck Sharp and Dohme and the Republic of Ecuador.

Starting in 2014, Alamuddin represented Canadian Al Jazeera English journalist Mohamed Fahmy who, along with other journalists, was being held in Egypt. He was eventually sentenced to three years in prison and lost a retrial in August 2015 before finally being pardoned by Egyptian president Abdel Fattah al-Sisi.

In August 2014, she declined a UN commission to look into possible violations of the rules of war in Gaza during the Gaza war of 2014.

In October 2014, she was hired in an attempt to repatriate the ancient Greek sculptures the Elgin Marbles. In May 2015, Greece decided to stop legal proceedings to recover the sculptures and dismissed her as their brief.

On 25 February 2014, the UK Attorney General’s Office appointed Alamuddin for the period 2014 to 2019 to the C Panel of the Public International Law Panel of Counsel.

In May 2014, Alamuddin was a signatory of UNICEF UK and Jemima Khan’s open letter that called for “action from UK Government to protect women and children”.

She became engaged to actor George Clooney on 28 April 2014. They had first met through a mutual friend in July 2013.

On 7 August 2014, the couple obtained marriage licences in the Royal Borough of Kensington and Chelsea in London. They married on 27 September 2014 in Venice’s city hall (at Ca’ Farsetti), following a high-profile wedding ceremony two days earlier, also in Venice. They were married by Clooney’s friend Walter Veltroni, former mayor of Rome. The wedding was widely reported in the media. In October 2014, it was announced that the Clooneys had bought the Mill House on an island in the River Thames at Sonning Eye in England at a cost of around £10 million.

In January 2015, Alamuddin began work on the recognition of the Armenian Genocide. She is representing Armenia on behalf of Doughty Street Chambers along with Geoffrey Robertson QC. She said Turkey’s stance was hypocritical “because of its disgraceful record on freedom of expression”, including prosecutions of Turkish-Armenians who campaigned for the 1915 massacres to be called a genocide. She is representing Armenia in the case against Doğu Perinçek, whose 2007 conviction for genocide denial and racial discrimination was overturned in Perinçek v. Switzerland (2013). A “minor internet frenzy” resulted from her bon mot prior to the 28 January 2015 hearing. In response to a journalist pestering her over what designer gown she would be wearing in court, she replied “Ede & Ravenscroft” – the tailors who make her court robes.

On 8 March 2015, Alamuddin filed a case against the Government of the Republic of the Philippines before the UN’s Working Group on Arbitrary Detention, a body under the United Nations Commission on Human Rights, for the continued detention of former Philippine president Gloria Macapagal-Arroyo. Arroyo was a sitting Pampanga congresswoman at the time. On 2 October, The United Nations Working Group on Arbitrary Detention later released its opinion that the detention of former President Arroyo “violates international law” and is “arbitrary on a number of grounds”.

On 7 April 2015, it was announced that she would be part of the legal team defending Mohamed Nasheed, former President of the Maldives, in his ongoing arbitrary detention. Nasheed was sentenced to 13 years in jail in March 2015 following what was characterized as a politically motivated trial. Amnesty International described his sentencing as a “travesty of justice”. Prior to visiting the Maldives, the local co-counsel working on the case was stabbed in the head, an indication of the danger and instability in the country. In January 2016, she gave a series of interviews about the UN-condemned trial and imprisonment of Nasheed and put forth efforts to support imposing sanctions on the Maldives. According to The Economist, she has “helped strengthen the backing of Britain’s prime minister, David Cameron, for the cause of Maldivian democracy.”

In June 2015, Alamuddin began work on the recently re-opened Hooded Men case brought by the Irish government against the British government in the European Court of Human Rights. She worked with Irish Minister for Foreign Affairs Charles Flanagan on the case, which concerned policies used by UK Prime Minister Edward Heath (1970–1974) in Operation Demetrius that included the illegal interrogation methods known as five techniques. In September 2018, the court rejected the final appeal in the case.

On 2 January 2015, it was reported by The Guardian that before Alamuddin was involved as Rapporteur in the case against Mohamed Fahmy, she had written a report in February 2014 for the International Bar Association’s Human Rights Institute (IBAHRI) that was critical of Egypt’s judiciary process. Alamuddin and others were warned that there was a strong possibility they would be arrested if they entered Egypt, as a result of the criticism.

In 2016, it was announced that Alamuddin would represent Azerbaijani journalist Khadija Ismayilova at the European Court of Human Rights. Ismayilova’s investigative work had resulted in her imprisonment. Following the trial, Ismayilova was released from prison and had her sentence reduced to a suspended three-and-a-half-year term.

In September 2016, Alamuddin spoke – for the first time at the United Nations – before the United Nations Office on Drugs and Crime (UNODC) to discuss the decision she made in June 2016 to represent Nadia Murad as a client in legal action against ISIL commanders. Alamuddin characterised the genocide, rape, and trafficking as a “bureaucracy of evil on an industrial scale” by ISIL, describing a slave market existing both online, on Facebook and in the Middle East that is still active today.

Alamuddin is the president of the Clooney Foundation for Justice, which she co-founded with her husband George Clooney in late 2016 to advance justice in courtrooms, communities, and classrooms around the world.

In February 2017, it was reported by the CBS talk show The Talk that Alamuddin was pregnant. Friend Matt Damon confirmed the pregnancy to Entertainment Tonight. In June 2017, she gave birth to fraternal twins.

In 2018, following the Stoneman Douglas High School shooting, the Clooneys pledged $500,000 to the March for Our Lives and said they would be in attendance.

Alamuddin, along with Ara Darzi, was involved in securing the release of two Reuters journalists, Wa Lone and Kyaw Soe Oo, from Myanmar on 7 May 2019.

In April 2019, she became a special envoy at the British Foreign and Commonwealth Office, advising the Secretary of State, Jeremy Hunt on global media freedom. In July 2019, she was appointed Vice Chair of the High Level Panel of Legal Experts on Media Freedom, convened by Lord Neuberger at the request of the UK and Canadian governments. The Panel is independent of government and formed of a group of leading international lawyers and has been constituted to ‘develop and promote legal mechanisms to prevent and reverse media abuses’. In September 2020, Clooney resigned as Special Envoy over the UK government’s intention to break international law over Brexit. She remains Vice Chair of the High Level Panel.

In 2019, Prince Charles launched the Amal Clooney Award to celebrate ‘incredible young women’.

In February 2020, she began to represent the Maldives in pursuing justice for Rohingya people at the UN International Court of Justice.