Three-times European champions Manchester United, arguably the biggest name in the draw, qualified as group winners while Club Brugge dropped in from the UEFA Champions League.
This was after the Belgian side finished behind Paris St-Germain (PSG) and Real Madrid.
Ajax Amsterdam’s consolation for exiting the UEFA Champions League at the group phase is a two-legged tie with Spanish side Getafe, while Inter Milan face Bulgarians Ludogorets.
“We’ve not had a lot of luck in the draw,” Getafe’s sporting director Angel Martin Gonzales said. “They’re a big side, but that helps us grow too.”
Two other clubs who failed to progress to the UEFA Champions League knockout rounds face off, with Benfica up against Shakhtar Donetsk.
AS Roma play Gent while former European champions FC Porto face Bayer Leverkusen, one of three German clubs in the draw.
Sevilla, the most successful club in Europa League history with five titles, play Romanian outfit CFR Cluj.
Eintracht Frankfurt face UEFA Champions League drop-outs Salzburg while VfL Wolfsburg take on Malmo.
Manchester United are one of three English clubs in the last 32 with Arsenal handed a testing tie against Greek club Olympiakos Piraeus.
Wolverhampton Wanderers face Espanyol in what will be their first clash with a Spanish club since losing 9-2 on aggregate to FC Barcelona in the 1959/1960 European Cup quarter-finals.
“It’s a big challenge for us to play against Arsenal, last year’s UEFA Europa League finalists,” Olympiakos coach Pedro Martins said.
“They may not have started well in the English Premier League (EPL) this season, but they have great players, are dangerous and deserve our respect.”
Scotland’s former European champions Celtic are up against Copenhagen while Rangers face Portuguese club Braga.
Sporting take on Turkish side Istanbul Basaksehir.
The draw was held at UEFA headquarters in Nyon, Switzerland.
The Full Draw:
Wolverhampton Wanderers vs Espanyol
Sporting vs Istanbul Basaksehir
Getafe vs Ajax Amsterdam
Bayer Leverkusen vs FC Porto
Copenhagen vs Celtic
APOEL vs Basel
CFR Cluj vs Sevilla
Olympiacos vs Arsenal
AZ Alkmaar vs LASK
Club Brugge vs Manchester United
Ludogorets vs Inter Milan
Eintracht Frankfurt vs Salzburg
Shakhtar Donetsk vs Benfica
VfL Wolfsburg vs Malmo
AS Roma vs Gent
Rangers vs Braga
*The matches are to be played on Feb. 20 and Feb. 27, while the first named clubs will play the first leg games at home.