The most unexpected outcome of the day came in Malta, where Floriana scored once in each half to beat Shamrock Rovers 2-0. Robert Muric gave the hosts the lead just before the break, with Mustapha Jah adding a second 11 minutes from time.
Shamrock, who had never lost in three previous games versus Maltese opposition before the game, managed just two attempts on target throughout the 90 minutes.
It did not help the League of Ireland outfit when midfielder Matthew Healy was sent off just before the hour mark after receiving two yellow cards in a matter of moments.
Despite participating in the UCL eight times before this, only once have Floriana managed to come out in a two-legged tie, which came 33 years ago.
The first goal scored in this season's competition was from Lincoln Red Imps' Nano, who converted a penalty in the 16th minute. He then assisted Manu Toledano 10 minutes later en route to a 3-1 win for his side over Andorran outfit Inter Club d'Escaldes.
A couple of debutants had mixed results on Tuesday. Azeri champions Sabah Baku got past Champions League regulars The New Saints 2-0 at home despite finishing the match a man down. Kauno Zalgiris' debut in the competition saw them lead for more than 50 in-game minutes versus Drita of Kosovo, but could not hold on. Blerim Krasniqi's equaliser eight minutes from time saw the game end 1-1 in Kaunas.
The other debutant, Atert Bissen, were not as lucky, losing 2-1 away to KI.
Vikingur strike late to claim victory
The last match of Tuesday saw Vikingur Reykjavik strike late to defeat Hungary's Gyor 1-0 in the Icelandic capital. Nikolaj Hansen headed in the winner in stoppage time to give Vikingur a key first leg success.
Gyor, who ended Ferencvaros' seven-year streak as Hungarian champions, failed to register a single shot on target in the match as Vikingur were the side asking more questions.
Vikingur, who reached the knockout rounds of the UEFA Conference League in 2024/25, have never progressed from a two-legged tie in the UCL in five previous attempts.
Elsewhere, Ararat-Armenia got the better of Riga FC 2-0 at home to take a key step towards progression. It was the same result in North Macedonia, where Finland's KuPS Kuopio defeated Vardar.
In Bosnia, Borac Banja Luka drew 1-1 against Levski Sofia, having taken the lead nine minutes in via a penalty. The Bulgarians levelled the match just before the hour mark to pick up a draw in their return to the UCL 17 years on from their last appearance.
Northern Ireland's Larne edged Tre Fiori 1-0 in San Marino to take a lead back home. Matthew Lusty scored the only goal just before the break.
Kairat find way to claim win
Wednesday's action saw Kairat Almaty, who reached the league phase last season, beat Sutjeska 2-1 in Kazakhstan. The goals came late on at Almaty Central Stadium, with Lucas Africo putting the hosts in front 14 minutes before the end.
A volley from Marko Mrvaljevic drew Sutjeska level in the last minute of normal time, giving them their first goal against a Kazakh side at the third time of asking. However, they could not hold on for the draw as Marc Gual struck two minutes later to give Kairat the win.
The Montenegrins await their first victory in the competition, having failed to come out on top in their other five attempts.
Iberia 1999 made things difficult for themselves in their trip to Estonia, having led Flora Tallinn 2-0 in the opening quarter of the game. Yet, Flora drew level despite playing the final half an hour down a man. The Georgians were not to be denied though, with Bakari Kardava netting the winner to give them a 3-2 win on the road.
Other results on Wednesday saw CS Universitatea Craiova defeat ML Vitebsk 4-1 on their return to the competition after 33 years away. Petrocub and Egnatia played to a 1-1 draw in their match, with the Albanians playing down a man for the entire second half.
The second legs are next week Tuesday and Wednesday.