Sampdoria are back in the second tier of Italian football for the first time since 2011 after they finished bottom of Serie A last season.
Pirlo has been charged with bringing them straight back up, having signed a two-year contract.
This is Pirlo's third role in management following one-year spells in charge of Juventus and Turkish side Fatih Karagumuruk.
He led Juventus to Coppa Italia and Italian Super Cup triumphs in his sole season in charge and led Karagumuruk to seventh place before leaving last month.
The 44-year-old will come in as a replacement for Dejan Stankovic, who left at the end of last season.
Pirlo won the FIFA World Cup as a player with Italy in 2006 as well as numerous Serie A titles with Juventus and AC Milan.
