[3][4] Her father, Melvin Schlein, is an American academic and political scientist of Ashkenazi Jewish descent.

[4][5] Her mother, Maria Paola Viviani, is a professor of comparative public law at the University of Insubria.

[6] Originally, her paternal grandfather's surname was Schleyen; after arriving at Ellis Island, he changed it to Schlein.

[4] Her maternal grandfather was the Italian Socialist Party politician Agostino Viviani [it], senator from 1972 to 1979 and a member of the High Council of the Judiciary.

[11] In April 2013, Romano Prodi, former Prime Minister of Italy and president of the Democratic Party (PD), received in support less than 100 centre-left coalition electors and left the 2013 Italian presidential election campaign.

In response, Schlein gave life to the mobilisation campaign known as #OccupyPD, which criticised those behind Prodi's loss and opposed the formation of a grand coalition government, the Letta Cabinet.

[20][21][22] In February 2020, the PD's secretary Nicola Zingaretti offered Schlein the party presidency spot left vacant by Paolo Gentiloni.

[39] In December 2022, arsonists destroyed a car used by her sister, diplomat Susanna Schlein serving in Athens, prompting Italy's incumbent prime minister Giorgia Meloni to express her "profound concern".