Pan Am Flight 73 had originated in Bombay and landed at Karachi's Jinnah International Airport for a scheduled stopover at 4:30 AM on September 5, 1986. The aircraft carried 394 passengers and 9 infants, along with an American flight crew and 13 Indian flight attendants. A total of 109 passengers had disembarked at Karachi, and the first busload of fresh passengers was approaching the plane on the tarmac when four men dressed as Karachi airport security guards drove up in a van fitted with a siren and flashing lights. They rushed up the boarding ramp firing shots into the air. Two more men joined them, one carrying a briefcase full of grenades. Gunfire outside the plane killed two Kuwait Airways ground workers nearby.

The four hijackers belonged to the Abu Nidal Organization, a Palestinian militant faction. A US grand jury later concluded they had planned to fly the jumbo jet to Cyprus and Israel to pick up imprisoned Palestinian fighters. But the cockpit was empty. For roughly seventeen hours, the hijackers held their hostages, making demands and growing increasingly agitated. They separated passengers by nationality, collecting American and British passports first. The standoff dragged through the scorching Karachi day. When the aircraft's auxiliary power unit ran out of fuel and the cabin went dark, the hijackers opened fire on the passengers. More than twenty people were killed, including citizens of India, the United Kingdom, Italy, Pakistan, and Mexico.

Senior purser Neerja Bhanot, 22 years old, had already saved the flight by alerting the cockpit crew. During the ordeal, she helped passengers hide their passports to prevent identification by nationality. When the shooting began, she opened emergency exits and pushed passengers toward the escape slides. She was shot and killed while shielding three children from gunfire. Bhanot received posthumous honors from three countries: India's Ashok Chakra Award, its highest peacetime bravery decoration; the United States Special Courage Award; and Pakistan's Tamgha-e-Pakistan. She remains the youngest recipient of the Ashok Chakra, and a 2016 Bollywood film bears her name.

All four surviving hijackers were arrested in Pakistan, sentenced to death, and later had their sentences commuted to life imprisonment. The legal aftermath stretched across continents and decades. One hijacker, Zaid Hassan Abd Latif Safarini, was brought to the United States in 2001 and sentenced to 160 years in federal prison. Another suspect was reportedly killed in a US drone strike in Pakistan in 2010. As late as 2018, the FBI released age-progressed photographs of remaining wanted suspects. Victims and their families filed a US$10 billion lawsuit against Libya, which had supported the Abu Nidal Organization. The hijacking of Flight 73 reshaped airline security protocols worldwide and left permanent scars on families spread across four continents.