The fee is undisclosed for the 21-year-old, but his departure will bolster the Premier League club's available wage budget as they look to bring in some new blood in order to survive in the top flight once again next season.
The Spain under-21 international failed to make an impact during his short stay in South London, featuring just six times for the Eagles before a loan spell at FC Nurnberg in Germany.
Campana was signed by former Palace boss Ian Holloway during last summer's transfer window and his arrival was eagerly anticipated by the fans.
There is no denying that he has an impressive long shot and his passing game is very good, but the Spaniard quickly began to frustrate Eagles' fans due to his poor discipline and lapses in concentration.
Under Holloway, Campana was used to aid captain Mile Jedinak in the central midfield role. In attack, he was sensational at times. His deliveries from set pieces showed a lot of promise, as did his passing range and accuracy.
However, when under pressure - which Holloway's Palace often were - he seemed subdued and slow to track back, which could be the reason why he was quickly phased out of the starting eleven.
Campana was given a loan opportunity in the Bundesliga with FC Nurnberg. In 10 appearances, he notched one goal and seemed to have a more successful spell than his one in South London.
Sadly for the player, his departure will probably be seen almost as a positive for Eagles fans, whom expected a lot but received very little. His transfer to Sampdoria means Crystal Palace must look to bring in a central midfielder during the summer transfer window.
The Eagles were linked with Gylfi Sigurdsson last week. The Icelandic midfielder would have been a fantastic signing for the club, but he looks set to return to Swansea City. The Welsh club were also keen on Palace midfielder Jonny Williams, which would disadvantage the Eagles further if the Swans acted on this interest.
This, plus the departures of Campana and Kagisho Dikgacoi, means that it is vital that Palace sign a central midfielder to deputise alongside Jedinak.
The Australian has been talismanic for the Eagles in the last two years, but he can not do all the work himself. The acquisition of utility man Joe Ledley in January 2014 means that there is some central midfield cover available, but not enough for a 38-game Premier League season.
If Palace are to stand any chance of survival this year, they need to bring in a central midfielder to provide a strong base to the team at Selhurst Park. Obviously, more signings than just a midfielder are needed - but recent news and rumours mean that a partner for Jedinak is now vital.