Elected in 1976 to the General Council of Loire-Atlantique département, he subsequently became Mayor of Saint-Herblain, located in the western suburbs of Nantes, in 1977.

After the surprising victory of the "Plural Left" in the 1997 legislative election, he was not appointed to the government but was instead designated as president of the Socialist parliamentary group in the National Assembly, a position he held for the next 15 years.

Ayrault's appointment to the country's head of government prompted discussion within Arabic language mass media as to how to pronounce his surname.

"[6] During his time in office, Ayrault and his ministers introduced a raft of progressive measures, including a reduction in the retirement age from 62 to 60 for some categories of workers, cuts in ministerial salaries of up to 30%,[7] a rise in the minimum wage, the introduction of a 36-month rent freeze on new contracts in some urban areas, an extension of social rebates on energy, increased educational support for low-income families,[8] the introduction of a system of subsidised employment for young people between 16 and 25,[9] and the extension of an entitlement to free health care to an additional 500,000 people.

[10] Ayrault resigned on 31 March 2014, the day after the "Socialists suffered heavy losses in nationwide municipal elections",[11] and formally handed over to his successor Manuel Valls at the prime ministerial residence, the Hotel Matignon, on 1 April 2014.

[14] In September 2016, Ayrault took part in the formal signing ceremony for the Hinkley Point C nuclear power station, a controversial $24-billion Franco-Chinese investment project.

[16] When President Hollande published a list of bank deposits and property held by all 38 ministers for first time 2012,[17] Ayrault declared personal assets worth 1.5 million euros.