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.
Second leg
Montpellier won 3–2 on aggregate.
Udinese won 3–1 on aggregate.
Deportivo La Coruña won 2–1 on aggregate.
Leeds United won 4–1 on aggregate.
Newcastle United won 4–2 on aggregate.
Levski Sofia won 3–0 on aggregate.
Celtic won 3–0 on aggregate.
Celta Vigo won 6–3 on aggregate.
Roma won 7–1 on aggregate.
Parma won 6–2 on aggregate.
Juventus won 10–2 on aggregate.
West Ham United won 6–1 on aggregate.
Benfica won 2–1 on aggregate.
Bologna won 5–2 on aggregate.
Monaco won 6–3 on aggregate.