Dr Nusseibeh was born in 1949 in Damascus, Syria. He comes from the Nusseibeh family, a very old Jerusalem family. Among other things, this family is traditionally the key custodian of the Holy Sepulchre Church in Jerusalem. Nusseibeh studied Islamic philosophy at Oxford and Harvard. In 1978, he returned to the Palestinians of the West Bank. There he became a professor and later rector of Al Quds University in Jerusalem. Dr Nusseibeh became and remained active for the Palestinian cause, organising political committees during the first Intifada. Israel saw him as a threat, accusing Dr Nusseibeh of passing funds to the occupied territories. The moderate activist sought solutions that satisfied everyone. Together with Feisal Husseini, he discussed with Likud leaders in the 1980s. He later fell victim to fanatical Fatah supporters who opposed rapprochement with Israelis.

Dr Nusseibeh was in favour of forming two independent states. Pressure from Israel increased: his Holy Land Press Service was closed down and the widely read Monday Report soon stopped. In 1991, Dr Nusseibeh was arrested as an "agent of Iraq" even though there were no official charges. There were protests in the US, the UK and from Amnesty International. Under this pressure, Dr Nusseibeh was released. In 2001, he became a representative of the Palestine Liberation Organisation in Jerusalem. There, he made a plan for forming a Palestinian state in the West Bank and Gaza Strip. Here, many Palestinians disagreed, insisting on returning to their own territories. Dr Nusseibeh opposed the then prevailing Intifada in 2002, especially the use of suicide bombers.