Juve are seen by many as the favourites to land the trophy this season, but the Serie A giants face a huge task to overcome Diego Simeone's stern Atletico team over two legs.
It would be fair to say that Atletico are not the most entertaining team to watch, but the manner in which the capital giants continue to grind out results is extremely impressive.
As it stands, they are Barcelona's closest challengers in La Liga, with a total of 47 points leaving them second in the table. Simeone's side have lost two of their last three in the league, though, and only just edged past Rayo Vallecano on Saturday courtesy of a second-half Antoine Griezmann effort.
Atletico were thumped 4-0 by Borussia Dortmund in the group stages of this season's Champions League, but that proved to be their only defeat, with a total of 13 points seeing them finish second in Group A to advance to the last-16 stage of the competition.
Simeone's team have reached the final of the Champions League in two of the last five seasons, losing to bitter rivals Real Madrid in both 2014 and 2016. This is the fifth time in six seasons that the capital side have been present in the last-16 stage of the competition and they will be desperate to advance to the quarter-finals.
Last term, Atletico failed to progress from their Champions League group but went on to win the Europa League, beating Lokomotiv Moscow, Sporting Lisbon, Arsenal and Marseille to land the title.
Atletico have actually won four of their five last-16 ties at this stage of the competition, while they have been victorious in four of their eight two-legged knockout encounters with Italian clubs.
The Spanish giants are unbeaten in 12 home Champions League knockout matches, meanwhile, and have won their last five home games against Italian visitors, suggesting that Juve will find it difficult to pick up a first-leg advantage on Wednesday night.
Atletico are not going to blow the Italian champions away in the first leg, but they will be tight and compact with the view to collecting a positive result ahead of the return game in Turin next month.
Recent form: WWLWWD
Recent form (all competitions): DWWLLW
Juve continue to dominate Italian football, but there is no question that the Champions League is the trophy that the Old Lady really want. They reached the final in both the 2014-15 and 2016-17 season, but lost to Barcelona and Real Madrid respectively.
Not since 1996 have Juve won the European Cup, but they are considered by many to be the favourites this term. The likes of Barcelona, Real Madrid and Paris Saint-Germain will have something to say about that, though, and Atletico will also be extremely tough opponents in the round of 16.
This is Juve's 10th Champions League last-16 tie, winning six and losing three of the previous nine. The Italians beat Tottenham Hotspur at this stage of last season's competition but then lost to eventual winners Real Madrid in the quarter-finals, which was seen as a huge disappointment.
So often the bridesmaid, Juve have actually reached nine European Cup finals, losing a record seven, including all of their last five. They seem well-placed to challenge for the trophy this season, but knockout football has a knack of bringing up surprise results.
Massimiliano Allegri's side will enter this match off the back of a 3-0 win over Frosinone in Serie A on Friday night. Incredibly, Juve are yet to lose in the league this season and sit 13 points clear of second-placed Napoli at the summit, suggesting that yet another Serie A crown is already wrapped up.
Cristiano Ronaldo was signed last summer with the view to helping Juve win the European Cup. The Portuguese has incredible history in the competition, while he scored 22 goals in 31 games against Atletico during his time with the reigning European champions.
Ronaldo will certainly relish returning to the Spanish capital on Wednesday night and will be looking to add to the 21 goals that he has managed in all competitions this season. That said, the attacker has only struck once in the Champions League thus far this term.
Recent form: WWWLWL
Recent form (all competitions): WWLDWW
Alvaro Morata is likely to start against his former club, with Griezmann also featuring in the final third.
As for Juve, Juan Cuadrado is still out of action following knee surgery, but Allegri has managed to recover a number of defensive players in recent weeks.
Ronaldo will be joined in attack by Paulo Dybala - linked with a move away from the club in recent weeks - and Mario Mandzukic, with the latter returning to the club that he represented during the 2014-15 campaign.
Atletico Madrid possible starting lineup:
Oblak; Arias, Godin, Gimenez, Luis; Koke, Rodri, Thomas, Saul; Griezmann, Morata
Juventus possible starting lineup:
Szczesny; Cancelo, Bonucci, Chiellini, Sandro; Pjanic, Matuidi, Khedira; Ronaldo, Dybala, Mandzukic
Head To Head
Wednesday will bring just the third meeting between these two teams in European competition.
We say: Atletico Madrid 1-2 Juventus
Atletico are so difficult to overcome on home soil, but this Juve team looks capable of winning the competition this season. We fancy the Italians to edge out a narrow victory at the Wanda Metropolitano.