De Fanti was appointed by Sunderland owner Ellis Short in June along with chief scout Valentino Angeloni - who has remained his post - in a bid to transform the way the club went about transfer deals.
A Sunderland statement was released later on Friday afternoon confirming De Fanti's departure ahead of Saturday's visit of Southampton.
Since then the Italian has been responsible for bringing in 14 new players but that has led to Sunderland spending the majority of the campaign rooted at the foot of the Premier League.
The likes of Valentin Roberge, Cabral and Modibo Diakite have all been acquired under his watch as director of football and all have been unable to hold down a first team place under new boss Gus Poyet.
Not all of his signings have struggled. Goalkeeper Vito Mannone looks worth every penny of £2m, while Fabio Borini and Ki Sung-Yueng have been two of the better performers under Poyet.
Poyet is looking to make his own progress on the transfer front in a bid to revive Sunderland's fortunes, but De Fanti will no longer be part of the set up.
Sunderland have already added left-back Marcos Alonso this month and are on the verge of announcing the signing of Argentine defender Santiago Vergini. Brighton's Liam Bridcutt has also been on the radar.
* For more on Roberto De Fanti's departure read The Northern Echo.