Salameh was born in the Palestinian town of Qula during the British mandate, near the city of Jaffa, to a wealthy family in 1940. His father, Hassan Salameh, was a commander who was killed in battle fighting against Israel in the 1948 War. Salameh was educated in Germany and is thought to have received his military training in Cairo and Moscow.
According to several sources, Salameh served as a secret contact between the Palestine Liberation Organisation (PLO) and the Central Intelligence Agency (CIA) from 1970 until his death, agreeing not to assassinate U.S. citizens in exchange for financial and political support.
On January 22, 1979, Salameh was in a convoy of two station wagons headed to his mother's for a birthday party. A Mossad agent detonated 100 kg of explosive attached to the car by another agent. The detonation left Salameh conscious, but severely wounded and in great pain, having pieces of steel shrapnel embedded in his head and throughout his body. He was rushed to the American University Hospital, where he died on the operating table. Salameh's four bodyguards were also killed in the explosion.
Salameh was buried in Beirut after a public funeral ceremony attended by Yasser Arafat and about 20,000 Palestinians on January 24, 1979.