The first round of the 1999–2000 UEFA Cup began on 14 September 1999. The round included 38 winners from the qualifying round, 16 losing teams from the Champions League 3rd qualifying round, 3 winners of the Intertoto Cup and 39 new entrants. This narrowed the clubs from 96, down to 48 teams in preparation for the second round.
Seeding
| Group 1 | Group 2 | Group 3 | Group 4 | ||||
|---|---|---|---|---|---|---|---|
| Seeded | Unseeded | Seeded | Unseeded | Seeded | Unseeded | Seeded | Unseeded | 
| Group 5 | Group 6 | Group 7 | Group 8 | ||||
| Seeded | Unseeded | Seeded | Unseeded | Seeded | Unseeded | Seeded | Unseeded | 
| 
 | |||||||
| Group 9 | Group 10 | Group 11 | Group 12 | ||||
| Seeded | Unseeded | Seeded | Unseeded | Seeded | Unseeded | Seeded | Unseeded | 
Summary
Matches
| Steaua București  | 2–0 |  LASK Linz | 
|---|---|---|
| Ciocoiu  63' Dănciulescu  83' | Report | 
Steaua București won 5–2 on aggregate.
Wolfsburg won 3–2 on aggregate.
| Red Star Belgrade .svg.png.webp) | 0–1 |  Montpellier | 
|---|---|---|
| Report | Loko  6' | 
| Montpellier  | 2–2 | .svg.png.webp) Red Star Belgrade | 
|---|---|---|
| Ouédec  34' Delaye  52' | Report | Jelić  48' Bošković  55' | 
Montpellier won 3–2 on aggregate.
| Stabæk  | 1–0 |  Deportivo La Coruña | 
|---|---|---|
| Finstad  57' | Report | 
| Deportivo La Coruña  | 2–0 |  Stabæk | 
|---|---|---|
| Jokanović  37' Conceição  63' | Report | 
Deportivo La Coruña won 2–1 on aggregate.
Udinese won 3–1 on aggregate.
| Leeds United  | 1–0 | .svg.png.webp) Partizan | 
|---|---|---|
| Huckerby  55' | Report | 
Leeds United won 4–1 on aggregate.
| HJK Helsinki  | 0–1 |  Lyon | 
|---|---|---|
| Report | Vairelles  16' | 
Lyon won 6–1 on aggregate.
| Atlético Madrid  | 3–0 |  Ankaragücü | 
|---|---|---|
| Gamarra  43' Hasselbaink  43' Paunović  58' | Report | 
| Ankaragücü  | 1–0 |  Atlético Madrid | 
|---|---|---|
| Aksancak  85' | Report | 
Atlético Madrid won 3–1 on aggregate.
| Fenerbahçe  | 0–2 |  MTK Hungária | 
|---|---|---|
| Report | Kenesei  56', 60' | 
MTK Hungária won 2–0 on aggregate.
| Anderlecht .svg.png.webp) | 3–1 |  Olimpija Ljubljana | 
|---|---|---|
| Bajrektarevič  20' (o.g.) Radzinski  35', 66' | Report | Ekmečič  52' | 
| Olimpija Ljubljana  | 0–3 | .svg.png.webp) Anderlecht | 
|---|---|---|
| Report | Koller  64' Radzinski  69', 72' | 
Anderlecht won 6–1 on aggregate.
| Roda JC  | 2–0 |  Shakhtar Donetsk | 
|---|---|---|
| Doomernik  20' Zafarin  25' | Report | 
| Shakhtar Donetsk  | 1–3 |  Roda JC | 
|---|---|---|
| Benyo  32' | Report | Tchoutang  27' van der Luer  81' van Dessel  87' | 
Roda JC won 5–1 on aggregate.
| Bodø/Glimt  | 0–5 |  Werder Bremen | 
|---|---|---|
| Report | Pizarro  12', 75' Bogdanović  44', 54' Maksymov  59' | 
| Werder Bremen  | 1–1 |  Bodø/Glimt | 
|---|---|---|
| Aílton  76' | Report | Staurvik  36' | 
Werder Bremen won 6–1 on aggregate.
| Sporting CP  | 1–0 |  Viking | 
|---|---|---|
| Ayew  71' | Report | 
Viking won 3–1 on aggregate.
Lens won 4–3 on aggregate.
| Kaiserslautern  | 3–0 |  Kilmarnock | 
|---|---|---|
| Koch  29' Djorkaeff  75' Marschall  39' | Report | 
| Kilmarnock  | 0–2 |  Kaiserslautern | 
|---|---|---|
| Report | Djorkaeff  22' Ramzy  29' | 
Kilmarnock won 5–0 on aggregate.
| Helsingborg  | 1–1 |  Karpaty Lviv | 
|---|---|---|
| Jonson  85' | Report | Hetsko  17' | 
| Karpaty Lviv  | 1–1 |  Helsingborg | 
|---|---|---|
| Hetsko  90+2' | Report | Jonson  90' | 
| Penalties | ||
| Hetsko  Yevtushok  Mizin  Pavliukh  | 2–4 |  Jansson  R. Nilsson  Jonson  Markstedt  Jakobsson | 
2–2 on aggregate; Helsingborg won 4–2 on penalties.
| Lech Poznań  | 1–2 |  IFK Göteborg | 
|---|---|---|
| Żurawski  44' (pen.) | Report | Andersson  27' Mild  83' | 
IFK Göteborg won 2–1 on aggregate.
| Teplice  | 3–1 |  Ferencváros | 
|---|---|---|
| Frýdek  33' Kolomazník  54' Rízek  71' | Report | Tóth  15' | 
Teplice won 4–2 on aggregate.
| CSKA Sofia  | 0–2 |  Newcastle United | 
|---|---|---|
| Report | Solano  51' Ketsbaia  77' | 
| Newcastle United  | 2–2 |  CSKA Sofia | 
|---|---|---|
| Shearer  36' Robinson  88' | Report | Litera  29' Simeonov  90' | 
Newcastle United won 4–2 on aggregate.
| Gorica  | 0–1 |  Panathinaikos | 
|---|---|---|
| Report | Liberopoulos  14' | 
| Panathinaikos  | 2–0 |  Gorica | 
|---|---|---|
| Sigurðsson  38' Nasiopoulos  69' | Report | 
Panathinaikos won 3–0 on aggregate.
| Amica Wronki  | 2–0 |  Brøndby | 
|---|---|---|
| Dawidowski  22' Bosacki  69' | Report | 
| Brøndby  | 4–3 |  Amica Wronki | 
|---|---|---|
| Madsen  35', 76' Vragel  54' Christensen  78' | Report | Kryszałowicz  52', 68' Kukiełka  63' (pen.) | 
Amica Wronki won 5–4 on aggregate.
Vitesse won 2–0 on aggregate.
Grazer AK won 4–2 on aggregate.
| Levski Sofia  | 3–0 |  Hajduk Split | 
|---|---|---|
| Ivankov  16' (pen.) Bachev  33' Dimitrov  85' | Report | 
Levski Sofia won 3–0 on aggregate.
| Celtic  | 2–0 |  Hapoel Tel Aviv | 
|---|---|---|
| Larsson  25', 50' (pen.) | Report | 
| Hapoel Tel Aviv  | 0–1 |  Celtic | 
|---|---|---|
| Report | Larsson  63' | 
Celtic won 3–0 on aggregate.
| Lausanne-Sports .svg.png.webp) | 3–2 |  Celta Vigo | 
|---|---|---|
| Kuzba  20' Mazzoni  21', 57' | Report | Revivo  62' Karpin  66' (pen.) | 
| Celta Vigo  | 4–0 | .svg.png.webp) Lausanne-Sports | 
|---|---|---|
| McCarthy  11', 84', 90+2' Mostovoi  76' | Report | 
Celta Vigo won 6–3 on aggregate.
| Ionikos  | 1–3 |  Nantes | 
|---|---|---|
| 
 | Report | 
 | 
Nantes won 4–1 on aggregate.
Aris won 3–2 on aggregate.
| Monaco  | 3–0 |  St Johnstone | 
|---|---|---|
| Simone  69', 89' Trezeguet  72' | Report | 
| St Johnstone  | 3–3 |  Monaco | 
|---|---|---|
| Griffin  24' (pen.) Dasovic  33' O'Neil  75' | Report | Léonard  4' (pen.) Pršo  9' Legwinski  69' | 
Monaco won 6–3 on aggregate.
| Inter Bratislava  | 1–0 |  Rapid Wien | 
|---|---|---|
| Ľalík  45' | Report | 
| Rapid Wien  | 1–2 |  Inter Bratislava | 
|---|---|---|
| Zingler  65' | Report | Suchancok  45' Babnič  64' | 
Inter Bratislava won 3–1 on aggregate.
| Lokomotiv Moscow  | 3–0 |  Lyngby | 
|---|---|---|
| Kharlachev  20' Drozdov  43' Janashia  44' | Report | 
Lokomotiv Moscow won 5–1 on aggregate.
| Skonto  | 1–0 |  Widzew Łódź | 
|---|---|---|
| Astafjevs  31' | Report | 
| Widzew Łódź  | 2–0 |  Skonto | 
|---|---|---|
| Wichniarek  1' Gęsior  43' | Report | 
Widzew Łódź won 2–1 on aggregate.
| Roma  | 7–0 |  Vitória de Setúbal | 
|---|---|---|
| Aldair  12' Montella  13' Alenichev  15', 54', 75' Assunção  39' Delvecchio  73' | Report | 
| Vitória de Setúbal  | 1–0 |  Roma | 
|---|---|---|
| Makinwa  79' | Report | 
Roma won 7–1 on aggregate.
| Parma  | 3–2 |  Kryvbas Kryvyi Rih | 
|---|---|---|
| Di Vaio  13', 20' Baggio  67' | Report | Palyanytsya  5' Monaryov  74' | 
| Kryvbas Kryvyi Rih  | 0–3 |  Parma | 
|---|---|---|
| Report | Boghossian  36' Crespo  40' Di Vaio  67' | 
Parma won 6–2 on aggregate.
| Hapoel Haifa  | 3–1 | .svg.png.webp) Club Brugge | 
|---|---|---|
| Turgeman  18', 32' Sivilia  44' | Report | Jankauskas  65' | 
| Club Brugge .svg.png.webp) | 4–2 |  Hapoel Haifa | 
|---|---|---|
| Verheyen  20' Borkelmans  25' Janssen  52', 90' | Report | Roso  18' Turgeman  78' | 
5-5 on aggregate; Hapoel Haifa won on away goals.
| Torpedo Kutaisi .svg.png.webp) | 0–1 |  AEK Athens | 
|---|---|---|
| Report | 
 | 
| AEK Athens  | 6–1 | .svg.png.webp) Torpedo Kutaisi | 
|---|---|---|
| Report | 
 | 
AEK Athens won 7–1 on aggregate.
| Omonia .svg.png.webp) | 2–5 |  Juventus | 
|---|---|---|
| Kontolefteros  75', 86' | Report | Inzaghi  2', 17' Kovačević  22' Esnáider  24' Del Piero  82' | 
Juventus won 10–2 on aggregate.
West Ham United won 6–1 on aggregate.
| Slavia Prague  | 3–2 | .svg.png.webp) Vojvodina | 
|---|---|---|
| Petrouš  40' Došek  74' Zelenka  80' | Report | Belić  18' Bogdanović  47' | 
Slavia Prague won 3–2 on aggregate.
Mallorca won 3–1 on aggregate.
| Benfica  | 0–1 |  Dinamo București | 
|---|---|---|
| Report | Năstase  35' | 
| Dinamo București  | 0–2 |  Benfica | 
|---|---|---|
| Report | Maniche  25' Chano  72' | 
Benfica won 2–1 on aggregate.
| Ajax  | 6–1 |  Dukla Banská Bystrica | 
|---|---|---|
| Verlaat  25' (pen.) Reuser  26' Knopper  48' Machlas  50', 64' Wamberto  72' | Report | Verlaat  15' (o.g.) | 
| Dukla Banská Bystrica  | 1–3 |  Ajax | 
|---|---|---|
| Malatinský  45' | Report | Arveladze  47' Bobson  64' Laudrup  90' | 
Ajax won 9–2 on aggregate.
| Tottenham Hotspur  | 3–0 |  Zimbru Chişinău | 
|---|---|---|
| Leonhardsen  3' Perry  32' Sherwood  55' | Report | 
Tottenham Hotspur won 3–0 on aggregate.
| Bologna  | 2–2 |  Zenit Saint Petersburg | 
|---|---|---|
| Fontolan  39' Cipriani  74' | Report | Panov  35' Kondrashov  89' | 
Bologna won 5–2 on aggregate.
| Anorthosis .svg.png.webp) | 1–0 |  Legia Warsaw | 
|---|---|---|
| Engomitis  83' | Report | 
| Legia Warsaw  | 2–0 | .svg.png.webp) Anorthosis | 
|---|---|---|
| Mięciel  48' Czereszewski  67' | Report | 
Legia Warsaw won 2–0 on aggregate.
| Locomotive Tbilisi .svg.png.webp) | 0–7 |  PAOK | 
|---|---|---|
| Report | Georgiadis  16', 24' Sabry  43' Frousos  56', 63' Frantzeskos  68' Vryzas  69' | 
| PAOK  | 2–0 | .svg.png.webp) Locomotive Tbilisi | 
|---|---|---|
| Valencia  53' (pen.) Salpingidis  81' | Report | 
PAOK won 9–0 on aggregate.
| AB Copenhagen  | 0–2 | .svg.png.webp) Grasshopper | 
|---|---|---|
| Report | Bjur  50' (o.g.) Ekoku  82' | 
| Grasshopper .svg.png.webp) | 1–1 |  AB Copenhagen | 
|---|---|---|
| Magro  80' | Report | Daugaard  31' | 
Grasshopper won 3–1 on aggregate.
| Lierse .svg.png.webp) | 3–4 | .svg.png.webp) Zürich | 
|---|---|---|
| Van Meir  16' Huysegems  72' Zdebel  83' | Report | Jamarauli  2' Frick  57' Eydelie  86' Daems  90' (o.g.) | 
Zürich won 5–3 on aggregate.