He retained this post until 2003, when he became a member of the social-democratic party Democrats of the Left (DS) and run for mayor of Bari for the centre-left coalition.

[7] In January 2005, he was appointed delegate of the National Association of Italian Municipalities (ANCI) for policies for the South and, since 29 March 2007, coordinator of the mayors of metropolitan cities.

[10] At the end of 2009, rumors rose up around Emiliano's candidacy at the head of centre-left candidate for the presidency of Apulia in the 2010 Apulian regional election.

The Union of the Centre (UdC) refused to accept the candidacy of incumbent governor Nichi Vendola, a democratic socialist.

During his years as mayor, Emiliano promoted a new urban plan, with the aims of redevelop the municipal area especially in the suburbs, thanks to investments in the environmental and the transport sector.

This contrast reached its peak at the 2016 Italian oil drilling referendum, which was promoted and supported by Emiliano and opposed by Renzi.

[16] Moreover, during the campaign for the 2016 Italian constitutional referendum, concerning the Renzi's Senate reform, Emiliano supported the "No", in open opposition to the line of his party.

[17][18] On 21 February 2017, Emiliano announced his candidacy in 2017 PD leadership election, scheduled in April, where he would challenge Renzi.

[26] Following the primaries' victory of Emiliano, considered by Italia Viva (IV) too close to the political positions of the Five Star Movement (M5S), Renzi announced that his party would run separately from the centre-left coalition.

On 25 September, Emiliano was confirmed president of the region, gaining 46.8% of votes and defeating the centre-right candidate Raffaele Fitto with 38.9%.