Twice Europa League winners Porto will face two-times finalists AS Roma in a knockout phase playoff tie, while Jose Mourinho's Fenerbahce have been drawn to take on Anderlecht.
Porto, winners in 2003 and 2011, last met Serie A club Roma in a Champions League last-16 clash in 2019, in which the Portuguese side emerged victorious.
Fenerbahce scraped through the league phase -- placing 24th, the last qualification place, in the new 36-standings format -- and have been rewarded with a match against Anderlecht as Mourinho bids for a trophy in his first season in Turkey.
His side trails Galatasaray by six points in the Super Lig, and Fener's Istanbul rivals take on AZ Alkmaar. Ajax, champions in 1992, will meet Union SG and fellow Eredivisie side FC Twente play Bodo/Glimt of Norway.
The top eight sides automatically qualified for the round of 16 while the teams that finished ninth to 24th will compete in the two-legged playoffs.
Premier League sides Manchester United and Tottenham Hotspur, among the favourites to win the tournament, secured automatic qualification to the Europa League round of 16.
United and Spurs could face the winners of the tie between Midtjylland and Real Sociedad, or the winners of AZ vs. Galatasaray.
The first legs of the playoff round will take place on Feb. 13. The return legs will be staged the following week (Feb. 20).
Europa League playoff draw:
FC Twente vs. Bodo/Glimt
Union SG vs. Ajax Amsterdam
AZ Alkmaar vs. Galatasaray
Ferencvaros vs. Viktoria Plzen
Fenerbahce vs. Anderlecht
PAOK vs. Steaua Bucharest
Midtjylland vs. Real Sociedad
Porto vs. AS Roma