Seven British teams have made it to the first round
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Spurs will make their return to Europe against Slavia Prague in the Uefa Cup first round, while Hearts also face a Czech Republic side, Sparta Prague.
The first leg of Hearts' tie will be played at Murrayfield on 14 September, with the return leg on 28 September.
Scottish giants Rangers have been drawn to face Molde FK, of Norway, while West Ham face Italian side Palermo.
Newcastle travel to Estonia to play FC Levadia Tallinn, while Blackburn go to Austria to play FC Salzburg.
Northern Ireland's Derry City, who play in the Eircom League, face a glamour tie at French side Paris St Germain.
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Spurs, who missed out on a place in the Champions League after defeat against West Ham on the final day of last season, will play the first leg away, as will Hearts, who lost to AEK Athens in the Champions League qualifiers.
Tottenham sporting director Damien Comolli believes his club are in a good position to make an impact on the competition.
He said: "The players we have bought this summer have experience of European competition, and we also had six players at the World Cup.
"But you also need quality, luck and to stay injury-free to go far."
Fellow Londoners West Ham are also revelling in the prospect of European competition.
The club's managing director Paul Aldridge said: "We're excited, shown by the fact we have already sold 16,000 tickets for the first game.
"And that was before today and knowing who we would be playing. So there's a great appetite for Uefa Cup football, that's for sure."
Blackburn boss Mark Hughes will pit his wits against legendary Italian coach Giovanni Trapattoni, who is now in charge at Salzburg.
And he was in cautious mood after the draw. He said: "This is not the easiest of ties.
"However we feel if we can get into the group stages we can progress from there."
But Rangers will be happy with their draw, with their first leg against FK Molde being played in Norway.
Manager Paul Le Guen said: ""It was our preference to play away from home first, so we are happy we have that."
And Newcastle will be favourites to progress from their tie against FC Lavadia Tallinn after making their way through the InterToto Cup and the Uefa Cup qualifying stage.
Spanish side Sevilla are in the first-round draw and will aim to defend the title they won at the expense of Middlesbrough last year.
Schalke, semi-finalists in 2006, are also back in the hunt along with fellow German club Bayer Leverkusen, winners in 1988.
British teams in capitals; seeds in bold
Levadia Tallinn v NEWCASTLE
Molde FK v RANGERS
Sparta Prague v HEARTS*
FC Salzburg v BLACKBURN
WEST HAM v Palermo
Slavia Prague v TOTTENHAM
The first-round matches are played over two legs on 14 and 28 September.
A total of 40 teams will then advance to the group stages, where pools of five teams vie to reach the knockout stages.
The winner, runner-up and third-placed team from each group advance to the last 32 where they are joined by eight clubs knocked out of the Champions League.
The competition will culminate in the final at Hampden Park 16 May.
Full draw:
Chornomorets v Hapoel Tel-Aviv
Braga v Chievo
Levadia Tallin v Newcastle
Molde v Rangers
Standard Liege v Celta Vigo
Maccabi Haifa v Liteks Lovetch
Derry City v PSG
Hertha Berlin v Odense BK
Legia Warsaw v Austria Magna
Panathinaikos v Metallurg Zaporizhzhya
Lokomotiv Moscow v Zulte-Wargerem
Sparta Prague v Hearts*
Fenerbahce v Randers FC
SV Red Bull Salzburg v Blackburn
Schalke 04 v AS Nancy
Ethnikos Achnas v Lens
Liberec v Crvena Zvezda
AZ v Kayserispor
Rubin Kazan v Parma
Brondby v Eitracht Frankfurt*
Atromitos v Sevilla
Besiktas v CSKA Sofia
Vitoria Setubal v Heerenveen
Marseille v Mlada Boleslav
Atvidabergs FF v Grasshopers
Rapid Bucuresti v Nacional
Trabzonspor v Osasuna
Basle v Rabotnicki Kometal
West Ham v Palermo
Feyenoord v Lokomotiv Sofia*
SCP Ruzomberok v Club Brugge
FC Sion v Bayer Leverkusen
Partizan Belgrade v FC Groningen
FC Xanthi v Dinamo Bucuresti
Slavia Prague v Tottenham
IK Start v Ajax
Artmedia Bratislava v Espanyol
Wisla Krakow v Iraklis
Livorno v FC Superfund
Dinamo Zagreb v Auxerre.
* Teams to play first leg at home.