In 1965, a group of aviation history devotees formed the Pacific Northwest Aviation Historical Foundation with a singular purpose: recover and restore a 1929 Boeing 80A-1 that had been discovered abandoned in Anchorage, Alaska. The Boeing 80A-1 was one of the first aircraft designed specifically for passenger comfort, with an enclosed cabin, leather seats, and room for a flight attendant. The restoration consumed sixteen years of painstaking work. By 1968, the nascent organization had adopted the name "Museum of Flight" and rented space at the Seattle Center. But the founders wanted something permanent. Fundraising crawled through the late 1970s until a breakthrough came in 1983, when Boeing's original manufacturing plant, a two-story wooden structure known as the Red Barn, was restored and opened to the public. Built in 1909, the Red Barn is now a registered historic site that illustrates how early aircraft were built from wooden frames with fabric overlays.

A capital campaign launched in 1983 transformed the museum's ambitions. Four years later, Vice President George Bush joined four Mercury astronauts to cut the ribbon on the T.A. Wilson Great Gallery on July 10, 1987. The gallery's soaring volume holds more than twenty aircraft in dramatic suspended display. Its glass roof was engineered by Jack Christiansen, the same structural engineer who designed the roof of Seattle's Kingdome. In 1992, the museum added a Challenger Learning Center where students experience simulated Space Shuttle missions from a mock-up NASA mission control. The museum continued expanding: a 132-seat cafe and a 250-seat multipurpose banquet facility opened in 1994, and in June 2016, the Aviation Pavilion doubled the museum's exhibit space with a massive covered outdoor display area housing 18 of the collection's most iconic aircraft, including bombers that had previously been brought outside only seasonally.

The museum's collection of more than 150 aircraft reads like a timeline of powered flight. The Caproni Ca.20, the world's first fighter plane from World War I, is the only one ever built and it lives here. A Lockheed Model 10-E Electra was restored to match the aircraft Amelia Earhart was flying when she vanished over the Pacific. Boeing VC-137B SAM 970, the first presidential jet, served in the presidential fleet from 1959 to 1996 and is open for visitors to walk through. The prototype Boeing 747, City of Everett, registration N7470, made its maiden flight on February 9, 1969, and now rests in the Aviation Pavilion. A British Airways Concorde, G-BOAG, is one of only four Concordes displayed outside Europe. The museum's B-29 Superfortress, known as T-Square 54, flew combat missions in the Pacific theater of World War II, while a B-52G nicknamed "Midnight Express" served during Vietnam before its restoration and display in 2019.

The Museum of Flight serves more than 140,000 students annually through onsite and outreach programs that extend across Washington and Oregon. Raisbeck Aviation High School, a STEM school operated by Highline Public Schools in partnership with the museum and Boeing, opened in a new facility directly north of the Aviation Pavilion in 2013. Students walk past supersonic jets and World War II bombers on their way to class. The museum's Harl V. Brackin Library holds 66,000 books specializing in aerospace, while the Kenneth H. Dahlberg Research Center provides public access to millions of photographs and thousands of feet of manuscript materials. With over 465,000 visitors in 2024, $27 million in operating revenues, and an endowment valued at $72.9 million, the museum has grown from a volunteer rescue mission for a single biplane into the largest private air and space museum in the world.