Manchester United will face Barcelona in the Europa League play-off round in February in a repeat of the 2009 and 2011 Champions League finals.
The two clubs have had some titanic battles in the past and now they will look to get reacquainted after Barca finished third in their Champions League group while United trailed Real Sociedad to finish second in their Europa League group.
Erik ten Hag is hoping to guide United to Europa League success in his first season in charge at Old Trafford and beating the Catalan giants would clear a big hurdle.
Elsewhere, Juventus play host to Nantes as Massimiliano Allegri looks to the Europa League to salvage his season while Jose Mourinho's Roma are in action away at FC Salzburg, a year on from winning the inaugural Conference League.
The draw could arguably not have gone any worse for United who are forced into playing two extra games by virtue of their second-place finish in Group E, with Real Sociedad advancing as winners on goal difference.
Barca have arguably the best squad of those teams dropping from the Champions League into the Europa League and it will be a big test of United's resolve if they are to advance.
La Blaugrana have one of the most lethal marksmen in Europe in Robert Lewandowski who has taken no time to settle in La Liga, scoring 13 in 13 league games.
Ten Hag's United have no doubt improved since their nightmare start but Sunday's 3-1 loss at Aston Villa showed there are still weaknesses that must be corrected if they are to compete with the best in Europe - beating the Catalan side over two legs would be a statement win.
For the first time since the 2013/14 season, Juventus will be competing in UEFA's secondary competition after being dumped out of Group H by PSG and Benfica.
The Bianconeri have struggled domestically this season and that form has transferred over to their European efforts, with the Italian giants winning only one of their six matches - which included a defeat to Israeli outsiders Maccabi Haifa.
It means Allegri has come under pressure from certain quarters though four straight league wins, including a 2-0 triumph over Inter Milan in the Derby d'Italia on Sunday, have quietened the dissenters slightly.
They face French outfit Nantes who ended Group G second with three wins and three defeats - a draw that has been kind to Juve and a tie they must turn up in.
Last season, Mourinho showcased his knack for winning trophies yet again as his Roma side beat Feyenoord 1-0 to secure victory in the maiden Europa Conference League final.
Now, he is aiming to go one better and win the Europa League as he did while Manchester United manager in 2017, and his side have been drawn to face Austrian outfit FC Salzburg.
Roma finished six points behind Real Betis at the top of Group C and had to come from behind to beat Ludogorets 3-1 and finish ahead of them, avoiding the drop into the Conference League.
Salzburg managed a solitary win in their group stage of the Champions League, beating Dinamo Zagreb at home 1-0 and Roma's extra European experience may benefit them greatly - they are 6/4 to win with Salzburg 17/10, and a draw is .
The Europa Conference League playoff was also drawn on Monday with several teams vying for a tilt at silverware.
Belgian side Anderlecht finished second to West Ham in their group and will face Bulgarian outfit Ludogorets, who, as stated above, gave Roma a scare in the Europa League.
Last season's quarter-finalists Bodo/Glimt, who have been widely praised for their attacking football over the past few years and were in Arsenal's group, face Lech Poznan.
Italian giants Lazio are in the equation as well and they will take on defending Romanian champions CFR Cluj.