A veteran legislator in Italian politics and an activist for various reform policies, she was elected as one of four vice presidents of the Senate on 6 May 2008.
Bonino was elected to the Italian Chamber of Deputies in 1976 and reelected in 1979, 1983, 1987, 1992, 1994 and 2006. In 1975, she founded the Information Centre on Sterilisation and Abortion and promoted the referendum which led to the legalisation of abortion in Italy. In 1986, she was among the promoters of a referendum against nuclear energy that led to the rejection of a civil nuclear energy programme in Italy.
On 17 May 2006, Bonino was appointed as minister for international trade in the cabinet of Romano Prodi. She resigned from office on 7 May 2008 when she had been elected vice president of the Senate the previous day. In 2008, at the elections of 13 and 14 April, she was elected to a seat in the Senate, the second parliamentary chamber, on the list of the Democratic Party for the Piedmont constituency.
On 28 April 2013, she was sworn in as foreign minister in the government led by Enrico Letta.
Bonino was elected to the European Parliament in 1979 and re-elected in 1984 and 1999. She served as the Secretary of the Transnational Radical Party in 1993–94 and the party's president in 1991–1993. In October 1994, she was appointed head of the Italian Government delegation to the UN General Assembly for the "Moratorium on death penalty" initiative. From 1994 to 1999, she was European Commissioner responsible for Consumer Policy, Fisheries and the European Community Humanitarian Office (ECHO). In 1997, her field of competence was widened to include consumer health protection and food safety.
On 15 March 1999, together with all the Santer Commission, she resigned due to the accusations of fraud and mismanagement against commissioner Édith Cresson. The final report however leveled charges against most commissioners, including Bonino herself. In November 2002, she was appointed Head of the Italian Government delegation at the Inter-governmental Conference of the Community of Democracies in Seoul.
Along with Marco Pannella, another member of the Radical Party, Bonino has fought numerous battles for civil rights and individual liberty, mainly concerned with divorce, the legalisation of abortion, the legalisation of drugs, and for sexual and religious freedoms. She has fought for an end to capital punishment, against female genital mutilation, and the eradication of world hunger.
In June 1999, she obtained a historic percentage of votes (8.5%) in the European elections (vs. the usual 2–3% that Radicals got in the previous and subsequent elections). Her list (Lista Bonino) won seven of 78 Italian seats in this election.
Еmma Bonino supported the NATO intervention in Kosovo in the Spring of 1999. From 1999 to 2004, the Lista Bonino was non-affiliated. Since 2004, it is part of the ALDE group. In December 2001, she moved to Cairo with the objective of learning the Arabic language and culture. In March 2003, she started a daily review of the Arabic press on Radical Radio. In January 2004, she organized the "Regional Conference on Democracy, Human Rights and the role of the International Penal Court, the first for an Arabic country. She is currently a board member of the Arab Democracy Foundation.
Bonino was a board member of DARA (international organization) until December 2012. In 2016, she was appointed by Erik Solheim, the Chairman of the Development Assistance Committee, to serve on the High Level Panel on the Future of the Development Assistance Committee under the leadership of Mary Robinson.
Taking her background, one can infer she is a fervent pro-European, she reaffirmed it recently by signing the Soros letter ('As concerned Europeans') and calling for a stronger European integration.
Bonino is a member of the eminent international Council of Patrons of the Asian University for Women (AUW) in Chittagong, Bangladesh. The University, which is the product of east-west foundational partnerships (Bill and Melinda Gates Foundation, Open Society Foundation, IKEA Foundation, etc) and regional cooperation, serves extraordinarily talented women from 15 countries across Asia and the Middle East.
Bonino is a godmother of Countess Luana, elder daughter of Prince Friso and Princess Mabel of Orange-Nassau.
In 1999 Bonino was one of the two winners of the North-South Prize, an award that honors individuals with accomplishment in the protection of human rights, pluralistic democracy, and improvement of North-South relations.
For her battles and engagements with controversial issues, her engagement in the promotion of human rights and civil rights in the world, she received the "Open Society Prize 2004" and "Prix Femmes d'Europe 2004" for Italy.
She received the America Award of the Italy-USA Foundation in 2013.