Italian giants Inter visit Stjarnan in Iceland while Villarreal, Tottenham and Feyenoord also begin their UEFA Europa League play-off ties on the road.
With places in the group stage of the tournament up for grabs, the stakes will be high on Wednesday and Thursday as 64 sides do battle in crucial first-leg ties.
Stjarnan could not have hoped for a higher-profile draw after negotiating a way past Bangor City, Motherwell and Lech Poznan to the competition's play-offs.
Stjarnan top the table in Iceland's Urvalsdeild by three points and striker Veigar Pall Gunnarsson cannot wait to pit his skills against the 18-time Italian champions on Wednesday.
"To play with Stjarnan, my boyhood club, against a team [like Inter] is a dream come true. We have to believe there is always a chance," he is quoted as saying on UEFA's official website.
Inter, who did not play European football for the first time since the 1999-2000 campaign last term, could give competitive debuts to the likes of Nemanja Vidic, Pablo Daniel Osvaldo and Yann M'Vila.
No club has won Europe's second-tier club competition more than Inter. They have won it three times, in 1991, 1994 and 1998, while they were also runners-up in 1997.
Villarreal, who finished sixth in La Liga last season, begin their tie in Kazakhstan as they meet Astana, while Tottenham – fresh off a last-gasp 1-0 Premier League win at West Ham United on Saturday – go to Cyprus for a clash with AEL.
Tottenham have won the competition twice, in 1972 and 1984, the club's Premier League counterparts, Hull City, start with a tricky trip to Lokeren.
Another two-time winner, Feyenoord, are unbeaten in two Eredivisie matches so far in 2014-15 and will hope to continue that run when they face Zorya of Ukraine.
Fellow Dutch side PSV have started the new campaign even better, with two wins helping them to the top of the league. PSV host Belarusian outfit Shakhtyor on Thursday.
Real Sociedad - who reached the group stages of the Champions League last term – host Russian outfit Krasnodar, while Borussia Monchengladbach, two-time winners of the competition, travel to Bosnia to play Sarajevo in their first leg.
Two wins from as many games has Saint-Etienne sitting second in Ligue 1 and they will be full of confidence ahead of their trip to Karabukspor.
Fellow French side Lyon begin with a home clash against Astra of Romania.
Sparta Prague are in action against PEC Zwolle of the Eredivisie, while Panathinaikos host Midtjylland, Young Boys meet Debrecen and Qarabag do battle with Twente.
Four Croatian sides are also in action, as Hajduk Split and Dinamo Zagreb visit Dnipro Dnipropetrovsk and Petrolul Ploiesti respectively, while Split host Torino and Rijeka welcome the visit of Sheriff.
There are also four Russian teams involved, with Krasnodar joined by Lokomotiv Moscow and Rostov – who have away ties against Apollon and Trabzonspor, respectively – and Dinamo Moscow.
Dinamo play host to Omonia Nicosia in their first leg.
Legia Warsaw travel to Aktobe while another Polish side, Ruch Chorzow, battle Metalist.
Other ties see HJK face off against Rapid Wien, while Dinamo Minsk, Elfsborg and Zimbru are at home to Nacional, Rio Ave and PAOK respectively.
Zurich hit the road to tackle Spartak Trnava and Partizan clash with Neftci, and there are home ties for Asteras Tripolis, who meet Maccabi Tel Aviv, and Grasshopper, who play Club Brugge.
|Portland Timbers 1 San Jose Earthquakes 0: Jewsbury wins it in stoppage time|
|No move yet for Van Persie|
|Lloyd wins Golden Ball, Silver Boot awards|
|Mascherano: I never grabbed Banega|
|Dunga requested Brazil not appeal Neymar´s suspension|
|United States 5 Japan 2: Lloyd stars with hat-trick|
|Fiorentina deny Inter criticism|
|Nani relishing Fenerbahce opportunity|
|Newcastle hold talks over Northampton youngster|
|Cuadrado´s agent plays down Chelsea exit rumours|
|Liverpool´s Alberto set for Deportivo loan|
|Leverkusen suffer surprise defeat, Stuttgart hit six|
|Inter ´dismayed´ at Fiorentina vice-president´s Salah Twitter outburst|
|Blaszczykowski ruled out of Dortmund´s Asia tour|
|Gerrard gets the beers in for LA Galaxy fans|
|De Gea coy over Real links|
|Former Brazil star Carlos handed Delhi reins|
|Ciftci will not push through Celtic switch – agent|
|In-demand Mitrovic considering Roma offer|
|Lehmann calls on Cech to ´get over´ Chelsea|
|Marlos double sinks Monaco|
|Mauritius 0 South Africa 2 (agg 0-5): Bafana set up Angola qualifier|
|Keane relishing Gerrard arrival|
|Palace confirm Cabaye interest|
|Hamburg bring in Spahic after head-butt ban|
|Blatter hits out at France and Germany over World Cup votes|
|Sanchez: World Cup exit spurred Chile to Copa glory|
|Jojic makes Cologne switch, Santana move falls through|
|Carrillo keen to get going at Monaco|
|Micronesia thrashed 38-0 as Fiji triumph in Olympic qualifier|
|Schalke stunned by ´machine´ Caicara|
|MLS Review: Keane shines at Gerrard´s Galaxy unveiling|
|Counter-attacking the key for Japan|
|Jimenez happy at Atletico|
|Gerrard predicts ´successful future´ with Galaxy|
|Iniesta can´t see Real selling Ramos|
|Keshi sacked as Nigeria coach|
|Three finals, three defeats for Messi, Mascherano|
|Nani close to Fenerbahce move|
|Sampaoli revels in ´unbelievable joy´|
|Bravo: Copa victory a dream|
|Martino: Argentina should have won|
|Chile 0 Argentina 0 (4-1 on penalties): Hosts end trophy drought|
|Germany 0 England 1 (after extra time): England make World Cup history|
|Kenya 0 Ethiopia 0 (agg 0-2): Hosts sent out of CHAN qualifiers after second penalty miss|
|Dortmund put 17 past Olympians, Bremen hand out thrashing|
|Dinamo Zagreb confirm arrests of coach and club president|
|I didn´t know who Wimbledon guest Klopp was - Brown|
|LeBron James backs Liverpool captain Henderson for FIFA 16 cover.|
|Ramos: I am not negotiating with anyone|
|Valencia complete Mina swoop|
|United States v Japan: US seek final redemption|
|Hanousek consigns Celtic to defeat|
|Roma confirm Dzeko interest|
|Arsenal forward Podolski completes Galatasaray switch|
|Warm Dortmund welcome delights Tuchel|
|Silva vows to fight for Madrid place|
|Mancini hints at Shaqiri and Santon departures|
|Bojan raring to go after return from injury|
|Babel backs Firmino to shine at Liverpool|
|Falcao must wait to impress, warns Chelsea favourite|
|Bartomeu: Deal in place for Turan|
|Parejo re-signs with Valencia|
|MLS Review: Sounders return to winning ways|
|Klinsmann unhappy with USA performance|
|High hopes for Paraguay - Diaz|
|Gareca: More to come from Peru|
|Gerrard had European offers|
|Argentina out to spoil Chile´s party - Martino|
|Sampaoli: Chile won´t change style|
|Di Maria will come good at United - Rojo|
|Peru 2 Paraguay 0: Gareca´s men finish third at Copa|
|United States 4 Guatemala 0: Klinsmann´s men win comfortably|
|´I’d prefer no-one to know my name´ - Bassett|