Utrecht – who trailed 2-1 after the first leg – returned home and despite conceding an early goal, moved 4-3 ahead on aggregate thanks to a hat-trick from Zambia’s Jacob Mulenga.
But Differdange were well worth their win as late goals from Geoffrey Franzoni and Yannick Bastos handed them a stunning overall victory on Thursday.
Shimon Abuhatzira and Rayo scored doubles for Israel’s Maccabi Haifa as they won 8-0 at Khazar Lenkoran of Azerbaijan.
The second-leg triumph – which helped Maccabi to a 10-0 aggregate win – was the biggest from an Israeli club in the history of any European tournament.
Belgium’s Standard Liege won 3-1 in both legs to triumph 6-2 against KR of Iceland and Poland’s Lech Poznan beat Honka of Finland 5-2 on aggregate, thanks to a 2-1 second leg win, while Serbia’s Red Star Belgrade beat IBV 2-0 overall after a goalless second-leg draw in Iceland.
Also progressing to the third round were Latvia’s Ventspils, Slovan Liberec of the Czech Republic, Norwegian outfit Tromso, Minsk of Belarus, Switzerland’s Thun, Poland’s Slask Wroclaw, Hapoel Tel Aviv of Israel and Qarabag of Azerbaijan.
Swedish outfit Malmo also got through to the next stage after they thumped Scottish Premiership side Hibernian 7-0 at Easter Road.
Malmo won the first leg 2-0 and scored four before the half-time break in their thrashing on Thursday, which saw seven different players score.
Russian outfit Rubin Kazan edged Jagodina of Serbia 1-0, to win 4-2 on aggregate, while a 1-1 draw in Macedonia saw Croatia’s Hajduk Split defeat Turnovo 3-2 overall.
Other teams to have joy and qualify for the next stage of the competition were Chornomorets (Ukraine), Mladost (Montenegro), Botev Plovdiv (Bulgaria), Petrolul Ploiesti (Romania), Rijeka (Croatia), Dinamo Minsk (Belarus) and Dila (Georgia).
Scotland’s St Johnstone drew 1-1 with Norway’s Rosenborg, winning 2-1 on aggregate, while Turkey’s Trabzonspor thrashed Derry City 7-2 over the two legs.
Sweden’s Hacken upset Sparta Prague of the Czech Republic 1-0, to progress 3-2, while the former’s countrymen, Gefle, recorded a stunning win.
Gefle – who trailed Anorthosis of Cyprus 3-0 after the first leg – won 4-0 at home, with Jakob Orlov and Mikael Dahlberg scoring in the last five minutes for the victors.
Other teams to win their way to the third round were Pandurii Targu Jiu (Romania), Milsami-Ursidos (Moldova), Trencin (Slovakia), Minsk (Belarus), Aktobe (Kazakhstan), Zalgiris (Lithuania), Astra Giurgiu (Romania), Zilina (Slovakia) and Breidablik (Iceland).
Serbia’s Vojvodina, Norway’s Stromsgodset, Siroki Brijeg of Bosnia-Herzegovina, Kukesi of Albania and Greece’s Xanthi also progressed.