The 52-year-old trainer takes charge of Blucerchiati after the dismissal of Ciro Ferrara on Monday, and will work with new sporting director Carlo Osti
The Blucerchiati find themselves in 14th place in Serie A, just three points above the relegation zone, and have not won in their last three league games.
Coach Ciro Ferrara paid the price for the club's current situation and was shown the door on Monday, and Sampdoria have acted quickly to bring in Rossi.
The Blucerchiati have also parted ways with sporting director Pasquale Sensibile, who will be replaced by Carlo Osti.
Rossi has been without a team since he was dismissed by Fiorentina earlier this year for attacking Adem Ljajic during a 2-0 loss against Novara, and he even had to endure a three-month ban from football for his actions.
During his 22-year coaching career, the 52-year-old has led 10 teams, winning the Coppa Italia with Lazio in 2009.