Pasqualina Napoletano started her political career joining the Italian Communist Party in 1971, and was responsible for the women's section in Rome; in 1980, Napoletano was elected member of Lazio Regional Council, and also became group leader.
Between July 1989 and July 2009 she was member of the European Parliament. During that period she was member of the Group for the European United Left, member of the Socialist Group, member and Vice-Chair of the Group of the Party of European Socialists, Vice-Chair of the Socialist Group in the European Parliament. She was Vice-Chair of the Members from the European Parliament to the Joint Assembly of the Agreement between the African, Caribbean and Pacific States and the EEC (ACP-EEC), Vice-Chair of the Committee on Budgetary Control, Vice-Chair of the Committee on Regional Policy, Vice-Chair of the Delegation for relations with the Maghreb countries and the Arab Maghreb Union, member of the Committee on Women's Rights, member of the Committee on Development and Cooperation, member of the Members from the European Parliament to the Joint Assembly of the Agreement between the African, Caribbean and Pacific States and the European Economic Community (ACP-EEC), member of the Committee on Budgets, member of the Delegation for relations with the countries of South Asia and the South Asia Association for Regional Cooperation (SAARC), member of the Committee on Culture, Youth, Education and the Media, member of the Delegation for relations with the Maghreb countries and the Arab Maghreb Union, member of the Committee on Foreign Affairs, Human Rights, Common Security and Defense Policy, member of the Committee on International Trade, member of the Subcommittee on Human Rights, member of the Delegation for relations with the Maghreb countries and the Arab Maghreb Union (including Libya), member of the Delegation to the Euro-Mediterranean Parliamentary Assembly, member of the Committee on Foreign Affairs, member of the Delegation to the Euro-Latin American Parliamentary Assembly.