Manchester United and Paris Saint-Germain will meet for the third time in four seasons after they had been paired together in the last 16 of the Champions League on Monday.
In a contest that pits Lionel Messi and Cristiano Ronaldo against one other, PSG will host the first leg in February.
The other notable tie pits Atletico Madrid against Bayern Munich, while holders Chelsea will meet French champions Lille.
Messi relocated to Paris in August, just as Ronaldo returned to Old Trafford for a second stint.
United memorably defeated PSG in the last 16 in 2018/19, returning from a 2-0 down at home in the first leg to win the return leg 3-1 and advance on away goals.
Last season, the clubs met twice in the group stage, with the away team winning both times.
Mauricio Pochettino’s PSG finished second in their group behind Manchester City this season, despite the arrival of Lionel Messi, while Manchester United won Group F ahead of Villarreal.
Pep Guardiola’s City will face Villarreal, who defeated United on penalties in the Europa League final last season and qualified for the last 16 ahead of Atalanta.
Meanwhile, Liverpool will face Austrian champions Red Bull Salzburg, who are making their debut appearance in the knockout stage.
Real Madrid, the 13-time European champions, were drawn against Benfica, the two-time past European Cup winners, with the opening leg taking place in Lisbon.
Inter Milan will face Ajax, while Sporting Lisbon will face Juventus.