The move is no shock, with the Italian, appointed to that role in June 2013, arriving at the club only seven months ago when Paolo Di Canio was appointed as head coach.
De Fanti had remained at the Stadium of Light when Di Canio was sacked in September after 13 games in charge.
"The club would like to place on record its thanks to Roberto and wishes him well for the future," a Black Cats statement read.
The Wearside club signed 14 players under the guidance of De Fanti in last summer's transfer window, spending approximately £19m.
Sunderland's buys included AZ Alkmaar striker Jozy Altidore, Italy international Emanuele Giaccherini and Arsenal goalkeeper Vito Mannone.
But when Di Canio was dismissed, most of his backroom team - first-team coach Fabrizio Piccareta, goalkeeping coach Domenico Doardo, fitness coach Claudio Donatelli and physio Giulio Viscardi - all left the club.
Now managed by Gus Poyet, Sunderland have a crucial game at home to Sunderland on saturday.