The experienced tactician has agreed a deal with the Genoa-based club through to 2021.
He steps into a void created by the dismissal of Eusebio Di Francesco.
It was decided that change was required in the dugout following a dismal start to the 2019-20 campaign.
Sampdoria currently sit bottom of the Italian top-flight with just three points.
Di Francesco paid the price for those failings with his job after overseeing a run of six defeats in seven games.
Ranieri will now be charged with the task of delivering a reversal in fortune.
A statement on Sampdoria’s official website read: “President Massimo Ferrero and UC Sampdoria welcome Claudio Ranieri, who has joined the club as manager responsible for the first team until 30 June 2021.
“The president is looking for the technician, his staff and the team to do a good job based on commitment and passion.”
Ranieri has delivered plenty of passion in previous posts.
The 67-year-old is a seasoned campaigner who has been coaching since 1987, with over 30 years spent working all over the world.
A brief foray into international football back in 2014 saw him struggle to deliver the expected results with Greece.
It was after leaving that role that he ended up at Leicester.
Prior experience of life in England had been collected during a stint with Chelsea between 2000 and 2004.
He was, however, to enjoy his most memorable success with the Foxes.
Against all the odds, Ranieri oversaw a stunning Premier League title triumph in 2015-16, earning him a much-deserved Manager of the Season award.
He would only last at the King Power Stadium until February 2017, when he was relieved of his duties.
A third spell in England was spent at Fulham, but he lasted less than a season at Craven Cottage before heading home and eventually linking up with Roma for a brief spell.