Manchester United will face French side Saint-Etienne in the Europa League last 32, while Tottenham Hotspur meet Belgian team Gent.
United midfielder Paul Pogba is set to face older brother Florentin, who plays for the eighth-placed Ligue 1 side.
Spurs have never met Gent, who finished third in the Belgian top-flight last season, in a competitive fixture.
The first legs will be played on Thursday, 16 February, with the return legs on Thursday, 23 February.
The two Premier League clubs could not be drawn together as teams from the same nation are kept apart.
Tottenham, along with the other seeded teams, will be at home in the second leg.
Spurs were seeded after dropping down from the Champions League, while United were unseeded after finishing second in Group A.
But Jose Mourinho’s side are still favourites to win the competition with most bookmakers.
The Europa League final will be held at Stockholm’s Friends Arena on 24 May.
Full draw
Athletic Bilbao (Spain) v Apoel Nicosia (Cyprus)
Legia Warsaw (Poland) v Ajax (Netherlands)
Anderlecht (Belgium) v Zenit St Petersburg (Russia)
Astra Giurgiu (Romania) v Genk (Belgium)
Manchester United (England) v Saint-Etienne (France)
Villarreal (Spain) v Roma (Italy)
Ludogorets (Bulgaria) v FC Copenhagen (Denmark)
Celta Vigo (Spain) v Shakhtar Donetsk (Ukraine)
Olympiakos (Greece) v Osmanlispor (Turkey)
Gent (Belgium) v Tottenham Hotspur (England)
Rostov (Russia) v Sparta Prague (Czech Republic)
Krasnodar (Russia) v Fenerbahce (Turkey)
Borussia Monchengladbach (Germany) v Fiorentina (Italy)
AZ Alkmaar (Netherlands) v Lyon (France)
Hapoel Beer Sheva (Israel) v Besiktas (Turkey)
PAOK (Greece) v Schalke (Germany)