Babak pertama Piala UEFA 2007–2008 dimulai pada 20 September 2007, yang mempersempit klub menjadi 40 tim sebagai persiapan untuk babak grup.

Tim 1	Agregat	Tim 2	Leg 1	Leg 2
Grup 1
Midtjylland	1–5	Lokomotiv Moscow	1–3	0–2
Groningen	2–2 (3–4 p)	Fiorentina	1–1	1–1 (p.w.)
Rabotnički	1–2	Bolton Wanderers	1–1	0–1
AEK Athens	3–1	Red Bull Salzburg	3–0	0–1
Nürnberg	2–2 (a)	Rapid București	0–0	2–2
Grup 2
Everton	4–3	Metalist Kharkiv	1–1	3–2
Zenit Saint Petersburg	4–1	Standard Liège	3–0	1–1
Bayer Leverkusen	5–4	União de Leiria	3–1	2–3
Villarreal	6–1	BATE Borisov	4–1	2–0
Sion	4–7	Galatasaray	3–2	1–5
Grup 3
Atlético Madrid	9–0	Kayseri Erciyesspor	4–0	5–0
Tampere United	3–4	Bordeaux	2–3	1–1
Artmedia Bratislava	1–5	Panathinaikos	1–2	0–3
Sparta Prague	0–0 (4–3 p)	Odense Boldklub	0–0	0–0 (p.w.)
Empoli	2–4	Zürich	2–1	0–3
Grup 4
Sochaux	1–2	Panionios	0–2	1–0
Anderlecht	2–1	Rapid Wien	1–1	1–0
Paços de Ferreira	0–1	AZ	0–1	0–0
Sampdoria	2–2 (a)	AaB	2–2	0–0
Spartak Moscow	8–1	Häcken	5–0	3–1
Grup 5
Hammarby	2–5	Braga	2–1	0–4
AEL	3–2	Blackburn Rovers	2–01	1–2
Mladá Boleslav	1–1 (4–2 p)	Palermo	0–1	1–0 (p.w.)
Dinamo Zagreb	3–3 (a)	Ajax	0–1	3–2 (p.w.)
Lokomotiv Sofia	3–4	Rennes	1–3	2–1
Grup 6
Brann	2–2 (a)	Club Brugge	0–1	2–1
Bayern München	3–0	Os Belenenses	1–0	2–0
Aberdeen	1–1 (a)	Dnipro Dnipropetrovsk	0–0	1–1
Heerenveen	6–8	Helsingborg	5–3	1–5
Toulouse	1–1 (a)	CSKA Sofia	0–0	1–1
Grup 7
Litex Lovech	1–4	Hamburg	0–1	1–3
Sarajevo	1–8	Basel	1–2	0–6
Austria Wien	4–2	Vålerenga	2–0	2–2
Hapoel Tel Aviv	1–0	AIK	0–0	1–0
Aris	2–2 (a)	Real Zaragoza	1–0	1–2
Grup 8
Dinamo București	2–2 (a)	Elfsborg	1–2	1–0
Tottenham Hotspur	7–2	Anorthosis Famagusta	6–1	1–1
Lens	2–3	Copenhagen	1–1	1–2 (p.w.)
Getafe	3–3 (a)	Twente	1–0	2–3 (p.w.)
Dyskobolia Grodzisk	0–2	Red Star Belgrade	0–1	0–1

¹ Pertandingan ini dimainkan di Panthessaliko Stadium di Volos karena lapangan AEL (Alkazar Stadium di Larissa) tidak memenuhi standar UEFA.

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Panathinaikos menang agregat 5–1.

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Agregat 2–2. Nürnberg menang gol tandang.

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Tottenham Hotspur menang agregat 7–2.

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Lokomotiv Moscow menang agregat 5–1.

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Helsingborg menang agregat 8–6.

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Atlético Madrid menang agregat 9–0.

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Hamburg menang agregat 4–1.

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Zürich menang agregat 4–2.

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Austria Wien menang agregat 4–2.

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Agregat 2–2. Elfsborg menang gol tandang.

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Agregat 1–1. Aberdeen menang gol tandang.

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Agregat 1–1. Toulouse menang gol tandang.

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Agregat 2–2. AaB menang gol tandang.

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Spartak Moscow menang agregat 8–1.

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Agregat 0-0. Sparta Prague menang penalti 4–3.

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Basel menang agregat 8–1.

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Agregat Dinamo Zagreb 3–3 Ajax. Dinamo Zagreb menang gol tandang.

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Villarreal menang agregat 6–1.

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Panionios menang agregat 2–1.

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Zenit Saint Petersburg menang agregat 4–1.

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Copenhagen menang agregat 3–2.

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AEK Athens menang agregat 3–1.

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Hapoel Tel Aviv menang agregat 1–0.

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Agregat Brann 2–2 Club Brugge. Brann menang gol tandang.

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Bayern München menang agregat 3–0.

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Galatasaray menang agregat 7–4.

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Everton menang agregat 4–3.

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Agregat Getafe 3–3 Twente. Getafe menang gol tandang.

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Red Star Belgrade menang agregat 2–0.

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Rennes menang agregat 4–3.

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Agregat Palermo 1–1 Mladá Boleslav. Mladá Boleslav menang penalti 4–2.

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Anderlecht menang agregat 2–1.

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Agregat Fiorentina 2–2 Groningen. Fiorentina menang penalti 4–3.

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Bolton Wanderers menang agregat 2–1.

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Agregat Aris 2–2 Real Zaragoza. Aris menang gol tandang.

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AEL menang agregat 3–2.

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Bordeaux menang agregat 4–3.

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AZ menang agregat 1–0.

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Braga menang agregat 5–2.

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Bayer Leverkusen menang agregat 5–4.

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