The former Cameroon international arrived at Everton from Chelsea at the start of the season, but made just eight Premier League starts under Roberto Martinez.
Eto'o's switch had been widely expected, and the striker was presented to Sampdoria fans on Sunday.
The 33-year-old has agreed terms on a two-and-a-half year deal at Samp, and Everton manager Roberto Martinez praised the forward on the club's official website.
"We thank Samuel for his efforts and for bringing his know-how to the team and to Finch Farm where he passed on some of his terrific experience to all of the young players in particular," he said.
"The memory of his performances in Europe stand out especially.
"On behalf of all Evertonians, we wish him well for the next chapter in his career."
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