A 3-0 first-leg victory away from home had all but settled this tie last week, but Paco Alcacer's header early in the second half made absolutely sure in a match largely devoid of drama.
Ludogorets started both halves of the match brightly, but after Diego Alves made a fine save to deny Roman Bezjak and then saw Mihail Aleksandrov blaze wide on the rebound in the 64th minute, their challenge was over.
The visitors did at least show promise in the early stages, with Vura's early free-kick touched over before Junior Caicara cut in from the right before pulling his shot wide.
Hristo Zlatinski then misfired from a good position and Ludogorets' early momentum began to dissipate without any reward.
Michel volleyed over for Valencia in the 16th minute before Javi Fuego's header was saved by Vladislav Stoyanov, and Federico Cartabia sent a free-kick into the wall.
As time ticked down in the first half, Zlatinski tried his luck from range but it was Valencia who went closest to scoring before the break with Dani Parejo's drilled free-kick striking the crossbar and bouncing down before the visitors scrambled it clear.
Ludogorets again started strongly but Vura's powerful lot shot was turned away for a corner after a good move.
The death knell came just before the hour mark as Cartabia dinked in a fine cross from deep on the left and Alcacer redirected it into the far corner.
Bezjak should have done better after some fine attacking play left him clear in front of goal but after Alves turned the ball away, the curtain came down on Ludogorets' best European campaign to date.