In 1938, he was born in the city of Safed.
After 1948, he moved to Alexandria, Egypt, with his father, to finish his studies at Alexandria University's Department of Business Administration, and then to the United States, where he earned Master's and Doctorate degrees in Business Administration from the Wharton International Institute of Management at the University of Pennsylvania.
He founded various businesses and served as an economic and administrative counselor to several Arab countries. He also taught at the American University of Beirut, where he rose to the position of Dean of the Faculty of Economics. He also worked at the American University in Cairo.
He served as an advisor to the late President Yasser Arafat. He returned to Gaza after the establishment of the Palestinian National Authority and was elected as a delegate of Khan Yunis and named Minister of Planning and International Cooperation. He was also named Deputy Prime Minister and Minister of Media and Information by Ahmed Qurei's government.
In January 2020, Palestinian President Mahmoud Abbas selected Nabil Shaath as his envoy, and he was removed from his duties as director of the Palestine Liberation Organization's Expatriate Department. On August 18, 2020, Palestinian President Mahmoud Abbas gave the Grand Star of the Order of Jerusalem to Nabil Shaath.