Lazio, serving the second of a two-game stadium ban, may not have had their fans to cheer them on but for 70 minutes they put up a determined fight to overcome the first-leg deficit, and Senad Lulic's goal just after the hour mark gave them hope.
But as they piled forward in search of a second, Caner Erkin's powerful equaliser - their first shot on target - ended Italian hopes and put Fener into the final four of a European competition for the first time.
Lazio dominated the first half and every chance of note was created by the hosts.
Early on, Antonio Candreva cut in from the left before firing a decent effort between two defenders but his shot was straight at Volkan Demirel.
Anderson Hernanes then tested the goalkeeper with a fierce free-kick which caught Demirel slightly wrong-footed.
He recovered to block the ball on the line but initially fumbled it, only just taking it off the toes of Libor Kozak on the line.
Candreva was then close to scoring something spectacular, hitting Lulic's low cross first-time on the volley and sending it narrowly over the crossbar.
Cristian Baroni was then booked for bringing down Ederson right on the edge of the area but Hernanes's free-kick was disappointing, going straight into the wall.
Fenerbahce never quite got it clear, however, and the ball eventually found its way back to Hernanes, whose curling effort from the edge of the area worried Demirel before going wide.
Ederson made room inside the area but his shot on the angle was blocked by Demirel's feet.
As the half ended, Hernanes' bouncing shot was fumbled and this time Kozak was booked for striking Demirel on the follow-up, although the goalkeeper seemed to make the most of it.
The pattern continued in the second half and barely two minutes after the restart Kozak had a great chance to get Lazio back into the game, heading over from Candreva's cross.
Demirel was the centre of attention again just before the hour mark, fumbling Stefan Radu's drilled shot and then needing the help of Joseph Yobo to deny Kozak's follow-up.
But a goal arrived moments later when Candreva whipped in a curling cross from the right after a quick free-kick and Lulic headed home powerfully at the far post.
Fenerbahce were rocking now and a rash challenge from Erkin on Candreva earned him a booking which will rule him out of their next European match.
But then there was a harsh booking for Lulic, who caught Yobo in the act of shooting.
Lazio continued to pile forward, having been given fresh hope, but that gave Fener space and with 18 minutes to go Erkin struck the killer blow.
Pierre Webo, with his back to goal on the penalty spot, rolled the ball out to the left and Erkin struck a thunderbolt beyond Federico Marchetti.
There was no atmosphere to kill inside the largely empty stadium but the wind was taken out of Lazio's sails either way.
Sergio Floccari headed a decent chance wide and moments later Kozak was replaced, a key danger man taking his leave.
Webo missed a good chance to kill them off completely when he mis-hit a half volley in space but Lazio could not find another goal, Lorik Cana coming closest with a powerful header at the back post which Demirel did well to palm over.