The Spanish side gave themselves a massive first-leg advantage last week by winning 3-0 in a smash-and-grab performance with 10 men and finished the job off in the return game thanks to Paco Alcacer's second-half header.
Like their meeting in Sofia, Ludogorets looked threatening on the flanks, but it was Valencia who appeared more likely to break the deadlock in the first half as Dani Parejo saw a free-kick come back off the crossbar just before the break.
Alcacer wasted one chance just after half-time, but he made no mistake with his next opportunity as he headed Valencia into a 4-0 aggregate lead in the 59th minute.
Ludogorets pressed for a late consolation, but the 2004 UEFA Cup winners held on with relative ease to confirm their place in the last eight.
Valencia coach Juan Antonio Pizzi insisted in the build-up that his side are targeting nothing less than Europa League glory this season, his confidence no doubt boosted by a dominant first leg that almost rendered the return clash an irrelevance.
The visitors enjoyed a lively start, however, and, after winning himself a free-kick in a dangerous position, Vura Misidjan saw a curling effort deflected just over the crossbar.
Ludogorets enjoyed a large share of possession as they looked to mount an unlikely comeback, but Valencia went close to increasing their aggregate lead in the 22nd minute as Vladislav Stoyanov saved a Javi Fuego header.
A mistake from Yordan Minev just past the half-hour mark saw Joao Pereira burst into Ludogorets' penalty area, but Cosmin Moti covered to great effect, bailing out his left-back with a well-timed sliding tackle.
The hosts ended the first period with great purpose and were agonisingly denied an opener on the night in stoppage time as Parejo's free-kick struck the bar.
Alcacer nearly gave Pizzi's men an ideal start to the second half as he latched on to Pereira's lofted pass, but he inexplicably failed to hit the target after charging into the area.
The 20-year-old made amends just before the hour mark, though.
Fede Cartabia fired in a teasing cross from the left and Alcacer met it with a glancing header, sending the ball past the helpless Stoyanov and into the bottom-right corner.
Mihail Aleksandrov almost got his name on the scoresheet a few moments later, but Diego Alves parried his close-range effort away from goal in acrobatic fashion.
The final stages resembled a training match for Valencia as they passed the ball around with little opposition from Ludogorets, and they comfortably progressed into the final eight of the competition.
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