The defender propped up with 18 minutes to go to prod home the winner to decide a narrow semifinal first leg against the Portuguese visitors
In a match which saw attacking action primarily against the woodwork, which was to be hit an amazing five times, Egemen Korkmaz's late controversial winner pushed the Turkish hosts that little bit closer to Amsterdam and a first-ever European final.
On a night of frustration for Benfica, substitute Nicolas Gaitan got closest with a shot against the post, with the visitors having it all to do at Estadio da Luz next week.
Despite the typically raucous atmosphere inside the Istanbul venue, it proved to be a cautious opening to the semifinal, with both sides happy to bide their time as Eduardo Salvio and Maxi Pereira ensured Benfica enjoyed the better of the two starts.
But given Fenerbahce's tidal wave of support, it wasn't long before it rallied at the other end with chances coming in quick succession.
Firstly, Webo's neat pass into Sow flashed narrowly wide, before Kuyt's superb cross was met wonderfully by the Ivorian striker who easily beat Jardel in the aerial challenge, but was unlucky to see his bullet header cannon back off the crossbar.
The first half drama began to ensue in additional time.
Ola John was adjudged to have fouled Gokhan Gonul approaching the penalty box, with Serbian referee Milorad Mazic immediately pointing to the spot. Up stepped Cristian Baroni, whose low penalty slammed against the post and away on the stroke of halftime, with the midfielder being dragged away in tears by teammates to complete a high-tempo first half.
The second, however, started in equally the same way for the Turkish outfit which was once more unable to penetrate the defense. With Cristian once more bringing a fine save out of the goalkeeper, followed by Raul Meireles' stinging effort, Kuyt ensured a third effort against the woodwork with a fine swivel and shot which Artur eventually reached.
It was then time for Benfica to test the vulnerable Volkan in the opposite goal, with Cardozo smashing a low effort towards the goalkeeper, before subsitute Nicolas Gaitan ensured the post was hit for the fourth time with a great effort from outside the box which left the custodian stranded.
Despite the chances at both ends, the deadlock would be broken, and fortuitously as the game hurtled towards the final quarter of an hour. From a corner, Korkmaz rose highest to head the ball yet again off the post with Melgajero at fault as the ball crossed the line before celebrations got going after the fifth official's goal award.
Fenerbahce held on to take command of the semifinal tie, as it looks to confirm a place in the Europa League final next week in the semifinal second leg at Estadio da Luz.