Former European champion Manchester United will take on AC Milan in the round of 16 of the Europa League while Arsenal will face Olympiakos and Tottenham plays the first leg at Dinamo Zagreb.
Ajax Amsterdam, the four-time European champions, will take on Swiss club Young Boys. Slavia Prague's reward for knocking out Leicester City is a two-legged tie against Scottish champions-elect Rangers.
European debutants Granada of Spain will face Norwegian club Molde while AS Roma face a tough tie against seasoned European contenders Shakhtar Donetsk.
Three-time semi-finalists Villarreal take on Dynamo Kyiv.
The ties will take place on March 11 and 18 with this season's final taking place in Gdansk where the eventual winners will take a place in next season's Champions League.
A clash between Milan and three-time European champions United will loom large over the last 16 for several reasons.
Some venues could change due to national restrictions on travel and quarantine during the COVID-19 pandemic.
Molde is unlikely to play in Norway for the second leg against Granada of Spain. Molde played its round-of-32 “home” game against Hoffenheim at Villarreal’s stadium in Spain.
First-leg games are on March 11 and return matches on March 18.
Draw for the last 16 of the Europa League following Friday's draw in Nyon:
Ajax v Young Boys
Dynamo Kiev v Villarreal
Roma v Shakhtar Donetsk
Olympiakos v Arsenal
Dinamo Zagreb v Tottenham Hotspur
Manchester United v AC Milan
Slavia Prague v Rangers
Granada v Molde