After a career in the social economy, Guillaume joined the Socialist Party (PS) in 1988 in its Rhône federation. She has held various responsibilities within the party, including that of president of the Socialists' national council between 2000 and 2003.
In the 2009 European elections, Guillaume was the second candidate on the PS list in the South-East region, and was elected to the European Parliament. She was reelected at the same position in 2014.
In addition to her committee assignments, Guillaume is a member of the Spinelli Group,[1] the European Parliament Intergroup on Artificial Intelligence and Digital,[2] the European Parliament Intergroup on LGBT Rights,[3] the European Parliament Intergroup on Disability,[4] the European Parliament Intergroup on Integrity (Transparency, Anti-Corruption and Organized Crime)[5] and the MEP Alliance for Mental Health.[6]
In 2012 Guillaume was responsible for immigration issues in the presidential campaign of François Hollande.[8]
From 2014 until 2019, Guillaume served as one of the Vice Presidents of the European Parliament, under the leadership of President Antonio Tajani. In this capacity, she was in charge of the parliament's transparency register and served as Vice Chairwoman of the Working Group on Information and Communication Policy.
Ahead of the 2022 presidential elections, Guillaume publicly declared her support for Anne Hidalgo as the Socialists’ candidate and joined her campaign team as diplomatic adviser.[10] In 2023, she publicly endorsed the re-election of the Socialist Party's chairman Olivier Faure.[11]