Northern Ireland outfit Cliftonville were undone by an Irishman as former Bohemians and Watford striker Dominic Foley scored twice for Belgian side Gent in a 2-0 home win.
Foley headed in the opening goal in the ninth minute before tapping in a second in the 63rd minute.
The second leg will be played at Windsor Park next Saturday but Gent will have to do without Christophe Gregiore while Cliftonville will be minus Declan O'Hara after the pair were sent-off for a bust-up in the final minute.
League of Ireland side Cork City will be disappointed to have only managed a 1-1 draw at home to Swedish side Hammarby.
City have knocked Malmo and Djurgardens out of European competition in recent years but Hammarby came from behind to claim a deserved away goal and advantage in the tie.
With Colin Healy, Gareth Farrelly and Joe Gamble all starting, Cork had three players with international experience in midfield but it was their most prized asset, Hull City target Roy O'Donovan, who gave them the lead as he fired into the net after being set up by Healy.
However, Hammarby got on terms when Chamon De Castilho's header deflected off Healy and into the net for the equaliser in the 57th minute.
The second leg takes place in Stockholm next Saturday.
In other notable results, former Champions League outfit Maccabi Hafia suffered a surprising 2-0 defeat at home to Romanian side Gloria Bistrita; while two-time former Cup Winners' Cup runners-up Rapid Vienna enjoyed a 3-1 home win over former winners of that competition Slovan Bratislava.