Since the first flight of the prototype in February 1963, a total of 120 of the 1,832 Boeing 727s built have been lost due to crashes, terrorist acts and other causes as of March 2024.

1960s August 16, 1965: United Airlines Flight 389, a new 727-100, crashed into Lake Michigan east northeast of Chicago's O'Hare Airport. The crew was told to descend to and maintain an altitude of , which was the last radio communication with the flight. Civil Aeronautics Board (CAB, the primary air mishap investigation body in the United States at the time) investigators were not able to determine why the airliner continued its descent into the water. All 30 people on board perished. November 8, 1965: American Airlines Flight 383, a 727-100, crashed on approach to the Greater Cincinnati Airport. Of the 62 people on board, only three passengers and one flight attendant survived. The investigation determined that the probable cause of the accident was the failure of the crew to properly monitor the altimeters during a visual approach into deteriorating visibility conditions. November 11, 1965: United Airlines Flight 227, a 727-100, departed LaGuardia Airport in New York City for a flight to San Francisco via Cleveland, Chicago, Denver, and Salt Lake City. Flight 227 crashed on landing at Salt Lake City International Airport, causing the deaths of 43 of the 91 people on board. The investigation determined that the cause of the accident was the captain's decision to approach the airport too steeply. February 4, 1966: All Nippon Airways Flight 60, a 727-100, was on approach to Tokyo's Haneda Airport at night when it crashed into the sea from the airport for reasons unknown, killing all 133 on board. November 15, 1966: Pan Am Flight 708, a 727-100, crashed near Dallgow, Germany (then East Germany) while on initial approach to Tegel Airport following an unexplained premature descent, killing the three crew. July 19, 1967: Piedmont Airlines Flight 22 collided with a twin-engine Cessna 310 shortly after departing Asheville Regional Airport in Asheville, North Carolina. All 79 passengers and crew on board the 727 and all three people in the Cessna died. November 12, 1967: An American Airlines 727-100 was flying over Alamosa, Colorado, when a bomb detonated in the rear baggage compartment, destroying three bags. The plane landed one hour and 45 minutes later. The FBI arrested the man responsible. February 16, 1968: Civil Air Transport Flight 010, a 727-100C, crashed on approach to Taipei, Republic of China. The flight carried 63 passengers and crew; 18 passengers, 3 crew and one person on the ground died. March 21, 1968: United Airlines Flight 9963, a 727-100QC operating on a cargo flight from O'Hare International Airport in Chicago to San Francisco, crashed shortly after takeoff; all three crew members survived. July 1, 1968: a hijacker on Northwest Airlines Flight 714 demanded to be taken to Cuba, landing at José Martí International Airport. July 4, 1968: TWA Flight 329 was hijacked out of Kansas City. September 22, 1968: Avianca Flight 101 was hijacked shortly after takeoff from Barranquilla. The hijacker demanded to be taken to Cuba, landing at Camaguey Airport. November 23, 1968: Eastern Air Lines Flight 73 was hijacked after taking off from Chicago-O'Hare, en route to Miami, Florida. The four hijackers demanded to be taken to Cuba, landing in Havana. January 5, 1969: Ariana Afghan Airlines Flight 701 crashed short of the runway near London Gatwick Airport; 48 passengers and crew and two people on the ground died. January 18, 1969: United Airlines Flight 266 crashed into Santa Monica Bay, California, after the pilots became disoriented following an unexplained electrical failure, killing all 38 on board. The crash led the FAA to require all transport aircraft to carry backup instruments powered by an alternate power source. April 8, 1969: LAN Chile Flight 160 crashed near Santiago, Chile, due to pilot error. There were no fatalities. June 4, 1969: Mexicana Flight 704 crashed near Salinas Victoria due to pilot error. All 72 passengers and seven crew members were killed. September 21, 1969: Mexicana Flight 801 crashed near Mexico City International Airport its during final approach, killing 27 of the 118 passengers and crew members on board.

1970s November 7, 1970: South African Airways Flight 307, a 727-100 (ZS-SBF), performed a landing at Cape Town International Airport with its nose landing gear retracted. December 28, 1970: Trans Caribbean Airways Flight 505 overran runway 09 at Harry S. Truman Airport on a flight from Isla Verde International Airport, killing 2 of the 55 people on board and injuring 51 of the 53 survivors July 30, 1971: All Nippon Airways Flight 58 collided with a Japan Air Self-Defense Force (JASDF) F-86F fighter jet, while en route from Chitose Airport to Haneda Airport in Tokyo, Japan. All 162 passengers and crew on board the 727 died, the fighter jet pilot survived. The crash of All Nippon Airways Flight 58 was the worst crash in aviation history at the time." September 4, 1971: Alaska Airlines Flight 1866, a 727-100, crashed into a mountain while on approach to Juneau, Alaska. A contributing cause involved the aircrew receiving erroneous navigational information for the approach. All seven crew members and 104 passengers died. November 24, 1971: Northwest Orient Airlines Flight 305 was hijacked by passenger D. B. Cooper while en route from Portland, Oregon to Seattle, Washington. After receiving a payment of $200,000 and four parachutes when he was in Seattle, he told the pilots to fly to Mexico, and jumped out of the aircraft from the aft airstair over Washington or Oregon. Cooper's fate is unknown. This incident led to the addition of a device named the "Cooper vane" on all 727s to prevent the airstair from being lowered while in flight. The 'Cooper' 727 continued in service until scrapped in the early 1990s in Missouri. May 5, 1972: Frederick Hahneman hijacked Eastern Air Lines Flight 175 en route from Allentown, Pa, to Miami, Fl. After receiving $303,000 and six parachutes he ordered the pilot to fly to Honduras, his birth country, where he jumped out and went on the run before finally surrendering.The Encyclopedia of Kidnappings by Michael Newton, Checkmark Books; 1st edition (April 1, 2002), 129The Dispatch, Lexington, N.C. 2 June 1972. Kurt Lassen, p12.The Morning Call. Frank Whelan. Sunday Call-Chronicle, 30 June 1985. May 25, 1972: an hour after a LAN Chile took off from Panama City, a pipe bomb detonated in the ice water fountain service compartment, causing a rapid decompression. The pilots managed to land safely in Montego Bay, Jamaica. August 16, 1972: During an attempted coup d'état, jets from the Royal Moroccan Air Force fired upon the 727 transporting King Hassan II of Morocco while he was traveling to Rabat. After the aircraft survived the attack, the king awarded it a medal of honor. February 21, 1973: Libyan Arab Airlines Flight 114, a 727-200 flying over the Sinai Desert was fired upon by Israeli air force aircraft as it was suspected of being an enemy military aircraft. Of 113 people on board, 108 died. September 15, 1974: Air Vietnam Flight 706 was hijacked by a former South Vietnamese army officer who ordered that it be flown to Hanoi. The pilots attempted to land at Phan Rang Air Base, but the aircraft crashed just short of it for unknown reasons. It was thought that the hijacker exploded grenades in the cockpit after the crew refused to comply with his demands. All 75 persons aboard died. December 1, 1974: TWA Flight 514, a 727-200 (registration N54328), crashed on Mount Weather while flying from Indianapolis, and Columbus, Ohio, to Washington Dulles International Airport in turbulent weather. All 85 passengers and seven crew members on board died. December 1, 1974: Northwest Airlines Flight 6231 crashed due to icing near Stony Point, New York. All three crew members died. June 24, 1975: Eastern Air Lines Flight 66 crashed on approach to John F. Kennedy International Airport; 113 people died. The cause was determined to be a microburst. November 12, 1975: Eastern Air Lines Flight 576 a 727-225, (registration N8838E) struck the ground about 282 feet short of runway 23 at the Raleigh-Durham International Airport, North Carolina, bounced and touched down on the runway, then slid to a stop off the right side of the runway 4,150 feet past the runway threshold. The accident occurred during an instrument landing system approach when the airplane encountered unexpectedly heavy rain while 100 feet above the ground. The airplane was damaged substantially from the first ground contact, both main landing gears and the No. 3 engine separated from the aircraft. The aircraft was repaired and returned to service.. Of the 139 persons aboard the airplane eight people were injured, one injured seriously; there were no fatalities. April 5, 1976: Alaska Airlines Flight 60 crashed on landing at Ketchikan International Airport after the aircraft overran the runway due to pilot error. One of the 50 people on board were killed. April 27, 1976: American Airlines Flight 625 crashed in St. Thomas, Virgin Islands, due to pilot error while trying to land on a notoriously tricky runway. 37 of the 88 people on board were killed. 10 September 1976: TWA Flight 355 was hijacked by five members of the "Fighters for Free Croatia" group and ultimately flown to Paris. 19 September 1976: Turkish Airlines Flight 452, a 727-200 (registration TC-JBH, named Antalya) on a domestic flight from Istanbul Yeşilköy Airport (IST/LTBA) to Antalya Airport (AYT/LTAI) struck high ground in the Karatepe Mountains during an attempted landing in Isparta instead of Antalya by pilot error. All eight crew and 146 passengers on board died. November 19, 1977: TAP Portugal Flight 425 overran the runway at Madeira Airport and plunged over a steep bank, bursting into flames; 131 of the 164 people on board died. May 8, 1978: National Airlines Flight 193 landed short of the runway at Pensacola Regional Airport coming down in Escambia Bay instead; three of the 58 passengers and crew on board died. September 25, 1978: Pacific Southwest Airlines Flight 182 crashed after colliding with a Cessna 172 aircraft in San Diego, killing all 137 people on board the 727 plus two on the Cessna and a further 7 on the ground for a total of 144 deaths. March 14, 1979: Alia Royal Jordanian Flight 600, a 727-200, crashed at Doha Airport in Qatar after an approach during a thunderstorm; 45 of the 64 passengers on board died. April 4, 1979: TWA Flight 841 went into a spiral dive over Saginaw, Michigan, after a slat failed to retract. The aircraft landed safely at Detroit with no loss of life. The pilots blamed the incident on mechanical failure, but the NTSB blamed the pilots. June 20, 1979: American Airlines Flight 293 was hijacked by Serbian nationalist and anti-communist Nikola Kavaja and flown back to New York City where he demanded and received a Boeing 707 to fly to South Africa but flew to Ireland instead. Kavaja planned to crash the 707 into the headquarters of the Yugoslav Communist Party, but he surrendered to Irish authorities who then turned him over to American authorities. November 15, 1979: American Airlines Flight 444 experienced an attempted bombing by the Unabomber. Although the bomb didn't detonate, it let off smoke. The pilots made an emergency landing at Dulles International Airport. Twelve passengers were treated for smoke inhalation. Ted Kaczynski was arrested in 1996.

1980s January 21, 1980: Iran Air Flight 291 crashed near Tehran, Iran; all 128 on board died.UK CAA Document CAA 429 World Airline Accident Summary (ICAO Summary 5/80) April 12, 1980: Transbrasil Flight 303, a 727-100C, crashed in Florianópolis, Brazil. 55 of the 58 people aboard died. April 25, 1980: Dan-Air Flight 1008, a 727-100 crashed in Tenerife. All 146 passengers and crew on board died when the aircraft hit terrain while circling.