The striker headed home midway through the second half to follow up his team's heavy away win last week and secure a spot in the last eight
The Spanish side gave itself 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 Alcacer's second-half header.
Valencia coach Juan Antonio Pizzi insisted in the build-up that his side is 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 it looked to mount an unlikely comeback, but Valencia went close to increasing its aggregate lead in the 22nd minute as Vladislav Stoyanov saved a Javi Fuego header.
The hosts ended the first period with great purpose and were agonizingly denied an opener on the night in stoppage time as Dani 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.
The final stages resembled a training match for Valencia as it passed the ball around with little opposition from Ludogorets, and the Spanish side comfortably progressed into the final eight of the competition.