Benfica are still just a point clear of Besiktas with one match to go as they joust for top spot in Group B.
The Portuguese cruised into a 3-0 lead inside barely half an hour but were pegged back as the Turks maintained their unbeaten record with two goals in the final seven minutes, including a penalty by former Sporting Lisbon and Porto man Ricardo Quaresma.
The draw means Benfica, European champions in 1961 and 1962, are still just a point clear of Besiktas with one match to go as they joust for top spot in Group B.
Benfica's late collapse meant Italian rivals Napoli could go two points clear with a win later Wednesday at home to bottom side Dynamo Kiev.
"The first half was fantastic and in the second we had chances to kill off the game, but we didn't get the fourth goal and handed them a way back with some lapses," said Benfica coach Rui Vitoria.
"It leaves a bitter taste that this draw means everything hangs on the final game."
That final game promises to be a cracker when Napoli, who beat Benfica in Italy 4-2, travel to Lisbon.
Besiktas supporters, having recently established a world crowd noise record at their Istanbul home, this time held what they dubbed the first "silent cheer", deploying sign language to raise awareness against racism and for the hard of hearing.
The hosts' fans had little to cheer in an opening half which saw their side swept away.
Vincent Aboubakar had a goal chalked off for offside for the Turks on four minutes before Benfica took the lead on nine minutes with Goncalo Guedes finishing off a flowing move, Eduardo Salvio providing the assist.
Before the half hour it was 2-0 to the visitors, as Nelson Semedo netted with a thumping left-footed shot.
Ljubomir Fejsa soon bagged another after former Fulham misfit Kostas Mitroglou and Salvio had first hit the woodwork to rub in early Portuguese superiority.
Besiktas recovered their poise after the break and Cenk Tosun pulled a goal back on the hour after Mitroglou had squandered a chance at the other end.
A Victor Lindelof handball gave Quaresma the chance to pull it back to 3-2 before Aboubakar finally had his reward as Quaresma picked him out for an unerring left-footed drive, the scorer earning a booking for a wild celebration amid deafening cheers on the terraces.