Liverpool FC completed a 4-1 aggregate victory against Slovenia's NK Olimpija Ljubljana with a 3-0 win at Anfield.
Led for the first time by new captain Steven Gerrard, first-half goals from Anthony Le Tallec and Emile Heskey were followed by a Harry Kewell strike shortly after half-time to put the 2001 winners through to the second round.
Myllykosken Pallo-47's hopes of overturning a 1-0 deficit in France against FC Sochaux Montbéliard were dealt a huge blow when Antti Okkonen was sent off for a second bookable offence on the stroke of half-time. Sylvain Monsoreau edged the eleven men ahead after 58 minutes before Francileudo Santos wrapped up a 3-0 aggregate win.
Newcastle United FC travelled to the Netherlands with a 5-0 lead over NAC Breda but on the night they could only add Laurent Robert's 86th-minute strike to their tally.
The game of the night was arguably in Belgrade, where FK Crvena Zvezda battled their way to a 4-3 win against Denmark's Odense BK, to take the tie 6-5. The hosts went ahead as early as the fourth minute courtesy of Nikola Zigic and although Odense replied through Nicolai Stokholm, the home side went further ahead with goals from Nemanja Vidic and Slavoljub Djordevic. But Steffan Hojer reduced the deficit and the visitors went ahead on away goals with 13 minutes to go when Stokholm scored again. Zigic ended the mammoth battle with the decisive goal in the 86th minute.
Da Silva Liedson's 48th-minute effort gave Sporting Clube de Portugal a 3-0 aggregate win against ten-man Malmö FF, who had Jon Inge Hoiland sent off. MTK Hungária FC were held 0-0 as they failed to overturn a 3-1 first-leg deficit against NK Dinamo Zagreb.
FC Aris Thessaloniki came from behind to see off CSF Zimbru Chisinau of Moldova 3-2 on aggregate. After a 1-1 draw in the away leg, Zimbru went ahead when Vladimir Shishelov struck after 18 minutes but Aris regained their composure and levelled 25 minutes later through Giorgos Koltsidas before Giannis Lazanas won the match four minutes from time.
Heart of Midlothian FC managed a goalless draw in Bosnia-Herzegovina against NK Zeljeznicar to progress 2-0 on aggregate while BV Borussia Dortmund became the first German team through with a 3-1 aggregate win against FK Austria Wien - Lars Ricken scoring the game's only goal in the 17th minute. AC Perugia made no mistake at home against Dundee F - leading 2-1 from the first leg in Scotland, the Italians were 1-0 winners on the night thanks to Massimo Margiotta's 71st-minute goal.
Wisla Kraków advanced after a 2-1 home win against eight-man NEC Nijmegen. NEC levelled the tie on aggregate with Mike Zonneveld's 33rd-minute strike and looked on course for a victory on away goals until Wisla levelled through Tomasz Frankowski on the stroke of half-time. Youssouf Hersi was shown a second yellow card in the 63rd minute and after Frankowski scored again, Patrick Ax and Zonneveld were sent off as Dutch tempers frayed.
RC Lens strode emphatically into the next round after a 6-0 aggregate defeat of FK Cementarnica 55. The French side followed up their 1-0 first-leg win with goals from Charles-Edouard Coridon, Daniel Moreira, John Utaka - a penalty, Adama Coulibaly and Dagui Bakari in a 5-0 success. Parma AC made similar light work of Ukrainian side FC Metalurh Donetsk. Level at 1-1 after the first leg, a goal either side of the break from Alberto Gilardino and Marco Marchionni's 72nd-minute third eased the Serie A side through.
Udinese Calcio were high-profile casualties at home against Austrian side SV Austria Salzburg, a 2-1 defeat sending them crashing out on away goals after a 2-2 aggregate draw. The hosts added to their first-leg lead through Valerio Bertotto but German legend Thomas Hassler reduced the deficit 25 minutes from time and Volkan Kahraman hit the winner in the 79th minute.
FC København put their supporters through the mill at home to Ferencvárosi TC before eventually prevailing on penalties. Thomas Roll missed a first-half penalty for the Danish side before Peter Lipcsei gave the Budapest giants what they thought was the winner seven minutes from time. Peter Nielsen levelled with a last-minute penalty for the hosts before Dragan Vukmir was sent-off to leave the visitors with ten men throughout extra-time.
Elsewhere, Samuel Eto'o helped himself to a hat-trick as RCD Mallorca beat APOEL FC of Cyprus 4-2 on the night and 6-3 on aggregate while Valencia CF struggled against Swedish side AIK Solna, needing a 70th-minute Miguel Mista strike to win the game on the night and complete a 2-0 aggregate win.