The round had begun on Tuesday and Wednesday with nine games, with the rest of the first leg clashes taking place on Thursday. Given the number of matches that occurred, it was inevitable that there would be a few shocking results.
One of the biggest ones came in Kosovo, where Malisheva - a club who is only 10 years old - pulled off a remarkable 2-0 victory against Hibernian.
Goals from Kreshnik Uka and Valmir Nafiu gave the side from a town of just 45,000 people a memorable versus the former European Cup semi-finalists.
The upsets kept on coming, as Romania's FCSB fell 3-2 at home to Auda. Having to battle back from a goal down twice, the Bucharest-based side looked to have avoided defeat.
That was before Auda, playing in just their fourth European season, found a winner in the 94th minute thanks to Kader Kone to stun the crowd. It was the first time that the side from Latvia scored three times in a European away game.
Ludogorets also lost on the night, with Israeli side Hapoel Tel Aviv coming out on top 2-0 in Hungary. The goals came at the end of both halves as the Israeli side, playing their firs European tie since 2014, defeated the 14-time Bulgarian winners.
The result leaves Ludogorets in danger of missing out on group phase football for the first time in 11 years.
Both Ukrainian teams earned draws versus more fancied opposition as well. Debutants LNZ Cherkasy held Gent to a goalless draw in their game, while Polissia Zhytomyr were involved in a thrilling 3-3 stalemate versus FC Kobenhavn.
The latter game saw both teams lead at some point, with the Danish side taking the lead late on only to be pegged back once more.
FC Nordsjaelland were beaten 1-0 away to GAIS thanks to a Matteo de Brienne strike shortly before the break. As for FC Noah, who made the Conference League knockout stage last term, they could only muster a 1-1 draw at Zimbru Chisinau.
Austrian duo prevail as Ajax cruise
While there were many head-turning results, some of Europe's big names still came out on top.
Both of Austria's Vienna-based clubs - Rapid Wien and Austria Wien - won their respective games. Rapid were tested against Andorra's FC Santa Coloma, eventually earning a 3-1 triumph. Austria were also given a challenge in the form of Liepaja, but the visitors came away with a 2-0 result against the Latvians.
As for four-time European Cup champions Ajax, they prevailed 4-1 in Serbia against Vojvodina.
Despite conceding an equaliser at the half-hour mark, the Dutch side did not lose their composure, regaining the lead before the break. They added two more in the second half, completing a solid performance against the club from Novi Sad.
Partizan Belgrade had no problems against 10-man UNA Strassen, beating the Luxembourgish team 4-0 at home. Dinamo Tbilisi also looked fairly comfortable as they got past Zalgiris Vilnius 3-0.
Former European Cup finalists Panathinaikos were made to work, with the Greeks edging Paksi of Hungary 2-1. Taking a 2-0 lead before the break, the away team looked well on their way to a solid win on the road.
The task got trickier when Daniel Bode got one back for Paksi, who have never progressed from a two-legged European tie when losing the home game. That was the furthest they got, giving them work to do in Athens nexst week.
In the champions path, Borac Banja Luka bounced back from Champions League disappointment with an impressive 3-0 defeat of Petrocub. The Bosnians outshot their guests 20-7 in the game as they head to Moldova next week looking to close the tie out.
ML Vitebsk also won 3-0 in their match, beating Sutjeska. It was the ninth time a Montenegrin side lost in Europe this season in as many games. Should the side from Niksic fall to defeat again next week, it would ensure their nation's clubs go 0-0-10 this term.
Flora Tallinn were the other team in the domestic champions path to win, edging The New Saints 1-0.
Next week will have the return legs, with 42 of the 49 games to transpire on Thursday.
View all of the UEFA Conference League second qualifying round results on Flashscore.