In 2013 Nencini was elected to the Chamber of Deputies among the ranks of the Democratic Party. From 28 February 2014 to 1 June 2018 he served as deputy minister of infrastructure and transport in the governments led by Matteo Renzi and Paolo Gentiloni.
In the 2018 general election he was elected senator in the uninominal constituency of Arezzo.
In 2019 he left the office of PSI secretary and was appointed president of the party.[2][3]