Manchester United will play Celta Vigo in the Europa League semifinals, with Ajax playing Lyon in the other tie.
United boss Jose Mourinho has indicated that the Europa League is his side's priority this season as victory would ensure qualification for next season's Champions League and face a first ever competitive meeting with the Spanish club.
Celta Vigo's Intertoto Cup win in 2000 represents their biggest trophy triumph.
United, who defeated Anderlecht 3-2 on aggregate in the last round, would become only the fifth club to win all three major European trophies if they succeed in the competition, after Ajax, Bayern Munich, Chelsea and Juventus.
Four-time European champions Ajax won the UEFA Cup -- the Europa League's predecessor -- in 1992.
Lyon, who have won Ligue 1 seven times since the turn of the millennium, won the Intertoto Cup in 1997 but have not won a major European trophy.
The sides last met in the group stage of the Champions League in 2011 when goalless draws were played out in both ties. Before that they met in 2002 with Ajax winning 2-1 at home and 2-0 away.
Ties to be played May 4 and 11:
Ajax vs. Lyon
Celta Vigo vs. Manchester United