Husseini was born in Baghdad son of Abdul-Qader al-Husseini. He studied in Cairo, Baghdad, Damascus. He was a founding member of the General Union of Palestinian Students (GUPS) in 1959;
Husseini went to work for the PLO upon its establishment in Jerusalem as deputy manager of the Public Organisation Dept, a post he filled from 1964 to 1965. He later received military training at the Damascus Military College after which he joined the Palestinian Liberation Army in 1967.
In 1979, Husseini founded and became chairman of the Arab Studies Society,
In the 1980s, he was repeatedly placed under house and city arrest and was imprisoned several times.
In 1982, he became a member of the Supreme Muslim Council in Jerusalem. Subsequently he served as a Palestinian spokesperson, head of the Jerusalem National Council/Palestine, head of Palestinian delegation to the Middle East Peace Conference, head of the Fatah faction in the West Bank, and Palestinian Authority Minister without Portfolio,
His last post was Palestinian Authority Minister for Jerusalem Affairs for which he was based in East Jerusalem. He died while trying to mend relations between the Kuwaiti government and PLO which were broken at the time of the 1991 Gulf War.
Husseini was considered a pragmatist. He argued that the best way to understand Israelis and try to convince them of the injustice suffered by the Palestinians was to get to know them. He taught himself to speak Hebrew and regularly appeared in radio and television shows in Israel to explain the Palestinians' point of view.