Italy international Gabbiadini scored just 12 goals in 60 appearances for Southampton despite making an impressive start after arriving from Napoli in January 2017, and hadn't made a single appearance since Ralph Hasenhuttl was appointed Southampton manager last month.
"Southampton Football Club can confirm that Manolo Gabbiadini has completed a permanent move to Sampdoria for an undisclosed fee," the club said in a statement.
"Everyone at the club would like to thank Manolo for his efforts during his time at St Mary's and wish him the very best for the future."
Gabbiadini's most memorable moment for Southampton came when he scored twice in their 2017 League Cup final defeat to Manchester United.
He also scored the crucial winning goal at Swansea on the penultimate day of last season as Southampton beat relegation from the Premier League by three points and helped send the Welsh side down to the Championship.
Gabbiadini's exit is part of Hasenhuttl's overhaul of his struggling squad as he fights to avoid the drop.
Steven Davis has joined Rangers on loan for the rest of the season, while Fraser Forster has reportedly been told he can leave.