The first round of the 2007–08 UEFA Cup began on 20 September 2007, which narrowed clubs down to 40 teams in preparation for the group stage.
|-!colspan="5"|Group 1|-!colspan="5"|Group 2|-!colspan="5"|Group 3|-!colspan="5"|Group 4|-!colspan="5"|Group 5|-!colspan="5"|Group 6|-!colspan="5"|Group 7|-!colspan="5"|Group 8|}
1 This match was played at Panthessaliko Stadium in Volos because AEL's Alcazar Stadium did not meet UEFA standards.
------------------------------------------------------------------------------------------------------------------------------------------------------------
Panathinaikos won 5–1 on aggregate.----Nürnberg 2–2 Rapid București on aggregate. Nürnberg won on away goals.----Tottenham Hotspur won 7–2 on aggregate.----Lokomotiv Moscow won 5–1 on aggregate.----Helsingborg won 8–6 on aggregate.----Atlético Madrid won 9–0 on aggregate.----Hamburg won 4–1 on aggregate.----Zürich won 4–2 on aggregate.----Austria Wien won 4–2 on aggregate.----Dinamo București 2–2 Elfsborg on aggregate. Elfsborg won on away goals.----Aberdeen 1–1 Dnipro Dnipropetrovsk on aggregate. Aberdeen won on away goals.----Toulouse 1–1 CSKA Sofia on aggregate. Toulouse won on away goals.----2–2 on aggregate. AaB won on away goals.----Spartak Moscow won 8–1 on aggregate.----Sparta Prague 0–0 Odense on aggregate. Sparta Prague won 4–3 on penalties.----Basel won 8–1 on aggregate.----Dinamo Zagreb 3–3 Ajax on aggregate. Dinamo Zagreb won on away goals.----Villarreal won 6–1 on aggregate.----Panionios won 2–1 on aggregate.----Zenit Saint Petersburg won 4–1 on aggregate.----Copenhagen won 3–2 on aggregate.----AEK Athens won 3–1 on aggregate.----Hapoel Tel Aviv won 1–0 on aggregate.----Brann 2–2 Club Brugge on aggregate. Brann won on away goals.----Bayern Munich won 3–0 on aggregate.----Galatasaray won 7–4 on aggregate.----Everton won 4–3 on aggregate.----Getafe 3–3 Twente on aggregate. Getafe won on away goals.----Red Star Belgrade won 2–0 on aggregate.----Rennes won 4–3 on aggregate.----Palermo 1–1 Mladá Boleslav on aggregate. Mladá Boleslav won 4–2 on penalties.----Anderlecht won 2–1 on aggregate.----Fiorentina 2–2 Groningen on aggregate. Fiorentina won 4–3 on penalties.----Bolton Wanderers won 2–1 on aggregate.----Aris 2–2 Real Zaragoza on aggregate. Aris won on away goals.----AEL won 3–2 on aggregate.----Bordeaux won 4–3 on aggregate.----AZ won 1–0 on aggregate.----Braga won 5–2 on aggregate.----Bayer Leverkusen won 5–4 on aggregate.