Pan Am Flight 103 was a regularly scheduled Pan Am transatlantic flight from Frankfurt to Detroit via a stopover in London and another in New York City. The transatlantic leg of the route was operated by Clipper Maid of the Seas, a Boeing 747-121 registered N739PA. Shortly after 19:00 on 21 December 1988, while the aircraft was in flight over the Scottish town of Lockerbie, it was destroyed by a bomb that had been planted on board, killing all 243 passengers and 16 crew in what became known as the Lockerbie bombing. Large sections of the aircraft crashed in a residential street in Lockerbie, killing 11 residents. With a total of 270 fatalities, it is the deadliest terrorist attack in the history of the United Kingdom.Following a three-year joint investigation by Dumfries and Galloway Constabulary and the US Federal Bureau of Investigation (FBI), arrest warrants were issued for two Libyan nationals in November 1991. In 1999, Libyan leader Muammar Gaddafi handed over the two men for trial at Camp Zeist, the Netherlands, after protracted negotiations and UN sanctions. In 2001, Abdelbaset al-Megrahi, a Libyan intelligence officer, was jailed for life after being found guilty of 270 counts of murder in connection with the bombing. In August 2009, he was released by the Scottish government on compassionate grounds after being diagnosed with prostate cancer. He died in May 2012 as the only person to be convicted for the attack.

In 2003, Gaddafi accepted responsibility for the Lockerbie bombing and paid compensation to the families of the victims, although he maintained that he had never given the order for the attack. Acceptance of responsibility was part of a series of requirements laid out by a UN resolution for sanctions against Libya to be lifted. Libya said it had to accept responsibility due to Megrahi's status as a government employee.During the First Libyan Civil War in 2011, former Minister of Justice Mustafa Abdul Jalil claimed that the Libyan leader had personally ordered the bombing, though this was later denied, while investigators have long believed that Megrahi did not act alone, and have been reported as questioning retired Stasi agents about a possible role in the attack.

Some relatives of the dead, including Lockerbie campaigner Jim Swire, believe the bomb was planted at Heathrow Airport, and not sent via feeder flights from Malta, as the US and UK claim. A sleeper cell belonging to the Popular Front for the Liberation of Palestine (General Command) had been operating in West Germany in the months before the Pan Am bombing.On the 32nd anniversary of the bombing, 21 December 2020, Abu Agila Mohammad Masud was charged in the US for having built the bomb that destroyed the aircraft and acting as a co-conspirator.