Defender Cosmin Moti saved two penalties in an extraordinary shootout win for the Bulgarians while Malmo overturned a deficit to Red Bull Salzburg to progress
At the Stadion Vasil Levski, defender Moti was the name on the lips of Ludogorets supporters as they defeated Steaua Bucharest 6-5 in a penalty shootout.
The Bulgarians forced spot-kicks by winning 1-0 on the night, but were up against it when goalkeeper Vladislav Stoyanov was sent off in the 119th minute for a second bookable offence.
Moti took the gloves and, after scoring Ludogorets' first penalty, saved Paul Pirvulescu's effort after Wanderson had missed for the hosts.
With sudden death needed, Coti then made the crucial stop from Cornel Rapa's spot-kick and duly raced to the home supporters to partake in wild celebrations as Ludogorets reached the group stages for the first time.
Joining them in Thursday's draw are Bundesliga outfit Bayer Leverkusen, who coasted past Copenhagen 4-0 at the BayArena to secure a 7-2 aggregate victory.
Leverkusen had effectively the put the tie to bed within the opening seven minutes as first Son Heung-min applied a cool finish from close range before Hakan Calhanoglu's free kick deflected home via the arm of Danny Amankwaa.
Amankwaa's evening went from bad to worse when he conceded a penalty for a foul on Tin Jedvaj on the half-hour mark and Stefan Kiessling confidently dispatched the spot-kick. The in-form forward then scored his second of the game in the 66th minute.
Elsewhere, Malmo overturned a 2-1 deficit from the first leg by beating Red Bull Salzburg 3-0 at the Swedbank Stadion.
Local hero Markus Rosenberg put the Swedish league leaders ahead from the spot after 11 minutes before Magnus Eriksson scored arguably the goal of the evening on the continent, flashing home a 30-yard volley just eight minutes later.
Malmo withstood a barrage of pressure from the Austrian champions in the second half before Rosenberg clinched the win with a calm finish six minutes from the end.