Tanguy Ndombele was the only survivor from Spurs' win over Manchester City in the Premier League, whilst Gareth Bale, Dele Alli and Carlos Vinicius returned along with goalkeeper Joe Hart.
Spurs threatened the lead in the first 11 minutes from a free-kick by Bale right in front of the area, but it came off the top of the net while Vinicius strayed wide later on.
Vinicius displayed more accuracy five minutes later after running through the centre of the defence to divert Alli's defensive-splitting pass beyond Ludogorets goalkeeper Plamen Iliev.
Ludogorets began feeling the heat from the host towards the half-hour mark, as Ben Davies volleyed against the outside post from the left-side.
Spurs bagged a second 12 minutes before halftime when Vinicius latched onto a lay-off from Alli to tap into the net after Iliev spilled Ndombele's initial shot.
Bale set in on goal ten minutes after the break following a first-time ball across the area by Matthew Doherty, but Iliev rushed from his goal-line to turn behind for a corner-kick.
The third goal arrived from in spectacular fashion as Iliev was caught out on 63 minutes after a superb long-range effort from Harry Winks following a throw-in on the near side crept in off the top of the post.
Ludogorets were handed another blow 72 minutes in when a cutback inside the area set up Lucas Moura to do the rest from close-range, as the lead extended four.
Three debutants from Spurs in the last ten minutes saw goalkeeper Alfie Whiteman, Harvey White and Dane Scarlett entering.
Scarlett was on the end of a clear chance right in front of goal, but Iliev came out to smother as the encounter ended 4-0 to Jose Mourinho's charges.