United qualified as Group A runners up, while Spurs were seeded after dropping from the Champions League.
Key Dates: United’s first leg will be played on 15 February, while Spurs will play the following day.
United will be played on Wednesday, as Saint-Etienne’s neighbours, Lyon, are playing at home in the Europe League, as well, that week.
Both the return legs will be played on 23 February.
Manchester United’s clash with Saint-Etienne will see Paul Pogba, who joined the Red Devils from Juventus in the summer for a world-record £93.2m fee, face his older brother, Florentin.
Europa League Draw: Complete Fixture
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)
United vs Saint-Etienne: History, Stats
The two sides have met before — in a two-legged European Cup Winners’ Cup tie in 1977-78.
The Red Devils were kicked out of the competition by Uefa after the first leg in France was disrupted by violence involving United supporters. They were reinstated on appeal and told to play their home game outside Manchester. United won 2-0 and progressed through, 3-1 on aggregate.
United have a great record against the French clubs, having lost just one of their last 16 matches, winning nine, and drawing six. Saint-Etienne are also the favourite opponent of Zlatan Ibrahimović, who has scored 14 goals in 13 games against the French club.
Spurs vs Gent
Tottenham Hotspur will make a short trip to Belgium to face the Group H runners-up, Gent, who qualified by winning their final match against Konyaspor.
Spurs have played Belgian opponents eight times in Europe — remaining unbeaten at home (W3 D1) but winless away (D2 L2). For the first time since 2013, we will have a new winner in the Europa League, as Sevilla, triumphant in each of the past three seasons, progressed to the Champions League last 16.