"AS Roma can confirm head coach Eusebio Di Francesco has left the club with immediate effect", the team said in a statement.
Roma president James Pallotta said his team had been "screwed again" after their UEFA Champions League elimination at the hands of Portuguese side FC Porto on Wednesday. "We all wish him well for the future".
Marega did give Porto the lead in the 52nd minute when he met a cross from Jesus Manuel Corona inside the box and produced a clinical finish to make it 2-1 (3-3 on aggregate).
The influential midfielder then suffered an injury towards the end of the first half, and Porto took advantage to force extra-time with Moussa Marega's finish, and then to ensure progress through Telles when penalties neared.
His first season was very successful as he led the side to a Champions League semi-final, including an epic comeback against Barcelona along the way.
An additional half-hour was required to settle an encounter that looked to be heading for a shootout before Telles tucked home from the spot on 117 minutes after a tug on Fernando by Alessandro Florenzi was spotted upon review.
Roma are fifth in Serie A, three points off the Champions League berths for next season, after falling 3-0 last weekend to bitter city rivals Lazio.
"We've got to accept it, even if the way it happened is bad to take", said De Rossi. "I know this isn't our best season and the job of a coach will always be tied to results".
Italian media reported that Claudio Ranieri, fired by English Premier League side Fulham last week, was a possible replacement.
Ranieri previously managed Roma between 2009 and 2011 - leading them to a second-place finish in 2010.