Prestwick's location is the explanation for almost everything. The airport sits one nautical mile northeast of the town of Prestwick and 32 miles southwest of Glasgow, with a microclimate of relatively low cloud incidence that earned it a place on the Atlantic Bridge route between Europe and North America in the Second World War. The RAF controlled trans-Atlantic flights from here. After the war, the connection stuck. The United States Air Force still uses Prestwick as a refuelling stop. So does the Royal Canadian Air Force. So does Air Force One, whenever an American president visits Scotland. The operations centre of Shanwick Oceanic Control, which manages air traffic across the entire northeast quadrant of the North Atlantic, sits close to the airport. Prestwick is, in air traffic terms, the place where Europe ends and the ocean begins.

Passenger facilities went up in 1938. The October 1946 USAAF diagram shows a 6,600 ft runway 14/32, with a shorter 4,500 ft runway 8/26 crossing just west of its midpoint. In 1958 runway 13/31 reached 7,000 ft, and in May 1960 the extension to 9,800 ft opened, capable of handling the new jet airliners. A parallel taxiway, a link road, and an all-new terminal building were opened by the Queen Mother in 1964. The extension caused a peculiar problem: the main road from Monkton into Prestwick now crossed the runway. For a time it was managed by a "level crossing" system - lights and barriers, like a railway - until a perimeter road was finished. Commercial transatlantic flights had started in 1945, when American Overseas Airlines began regular service from Prestwick to New York. Pan Am acquired AOA and used Prestwick as a stop between Europe and North America into the 1970s. BOAC used it too, between London and New York, in the late 1940s and 1950s.

Glasgow Prestwick Airport has a piece of cultural history nobody else in Britain can claim. In 1960, on his way home from US Army service in West Germany, Elvis Presley's transport stopped here to refuel. He stepped off the plane onto the tarmac. He had distant Scottish ancestry, but he had never visited Britain otherwise - and as far as the public record knows, this is the only time his feet touched British ground. (In 2008, the impresario Bill Kenwright claimed on BBC Radio 2 that Elvis had actually been smuggled into London for a day by Tommy Steele in 1958. The story is unverified.) For Prestwick the documented refuelling stop is enough. It is the only place in the United Kingdom where Elvis Presley is known to have set foot.

Until February 2016, part of the site was occupied by the Royal Navy's Fleet Air Arm as RNAS Prestwick, officially HMS Gannet, where three Sea King helicopters covered one of the largest search-and-rescue areas in the UK - from Ben Nevis to the Lakes to Northern Ireland and 200 nautical miles past the Irish coast. The crews featured in the Channel 5 documentary series Highland Emergency. In 2009 they broke records: 447 call-outs in a single year, 20 percent of all UK military SAR call-outs, making them the busiest SAR base in the country for the second year running. Prestwick also has darker chapters in its history. There was sustained controversy over the airport's use as a stop-over point for CIA extraordinary rendition flights. And it has occasionally hosted Top Gear stunts, including the test of whether four jet engines on a Virgin Atlantic Boeing 747 could lift a Ford Mondeo and a Citroën 2CV off the ground (they could).

The airport's accident record stretches across the jet age. On 28 August 1944, a USAAF Douglas C-54A Skymaster crashed into houses on the south side of the airport while attempting to land - all 20 on board and five people on the ground were killed. On 20 October 1948, a KLM Lockheed Constellation crashed on approach; all 40 aboard died. At 03:30 on Christmas morning 1954, a BOAC Boeing 377 Stratocruiser crashed on landing, killing 28 of the 36 passengers and crew - the public inquiry found pilot error was the cause, with the first officer's failure to turn on the landing lights as a contributing factor. On 17 March 1977, a British Airtours Boeing 707 crashed during pilot training and caught fire; all four crew survived. On 6 October 1992, a British Aerospace Jetstream 31 on a training flight crashed shortly after takeoff after simulating an engine failure; both occupants were killed. Each crash taught something. Each loss is remembered locally.

The 1992 purchase by Canadian entrepreneur Matthew Hudson is locally credited with saving the airport. Hudson initiated the construction of Prestwick's railway station on the existing Ayrshire Coast Line - making Prestwick the first Scottish airport with its own station, opened in 1994 and still owned by the airport itself rather than Network Rail. In 2001 Infratil bought the airport and in 2005 rebranded it with the slogan "pure dead brilliant" - straight from the Glasgow patter - which lasted until January 2014. A logo of a kilted man unconscious beside an empty whisky bottle was removed within weeks after the South Ayrshire Licensing Board ruled it trivialised excessive drinking. In November 2014 Donald Trump signed a partnership agreement making Prestwick the Scottish base for Trump Aviation Operations, serving his Turnberry resort 20 miles south. A 2014 petition from the Robert Burns World Federation to rename the airport "Robert Burns International" was ruled out by the Scottish Government. The Scottish Airshow returned in 2014 and ran with growing success until a 2019 dispute over funding. It was rebranded for 2023 as The International Ayrshow - Festival of Flight, organised by South Ayrshire Council. The airport itself remained in public ownership, with a 2021 sale to a European infrastructure investor falling through at the last hurdle. As of the most recent reporting the field continues to operate, still strategically essential, still controversial, still flying.