It was another desperately disappointing result for David Moyes' team that had been hammered 5-0 by the Portuguese side in Lisbon a fortnight ago.
They should still qualify for the next stage of the competition but they are certainly enduring a difficult time at the moment.
Everton edged a low-key first half without ever really looking like breaking the deadlock. Marouane Fellaini's early effort was saved by goalkeeper Julio Cesar while, at the other end, Angel di Maria's 20-yard shot was kept out by Tim Howard.
Yakubu shot wide in the 16th minute and Leighton Baines saw his shot blocked as Moyes' side continued to look the likelier team to score.
Di Maria looked dangerous for the visitors and he had a shot blocked before Tim Cahill was denied by Cesar in the 33rd minute.
However, the clearest first-half opening was created by Benfica four minutes before half-time when Fabio Coentrao's cross was headed towards goal by Santos Ramires.
The effort beat Howard but the ball came back off a post, and when Javier Saviola latched on to the rebound, he was denied by the keeper.
Struggling down in 13th place in the Premier League, Everton lost their way in the second half as Benfica grew in confidence.
Howard had to be at his best to keep di Maria's long-range effort out before Benfica, currently second in the Portuguese League, took the lead in the 63rd minute.
The visitors launched a swift counter-attack as di Maria and Saviola exchanged passes before the 27-year-old Argentinian, signed from Real Madrid in the summer, drilled a shot past Howard.
The game was over with 14 minutes remaining when Benfica doubled their advantage. Saviola was again at the centre of the move that led to the goal which came when Oscar Cardozo volleyed home after Ruben Amortim's initial effort had been deflected.
The only good news for Everton on another grim evening for the club came in the Greek capital where the two other teams in the group - BATE Borisov and AEK Athens - drew 2-2, the perfect result for Moyes' side.