Los Rojiblancos famously dumped the Reds out of the competition the season after they had beaten Tottenham to lift the title at Atletico's Estadio Metropolitano, one of three wins - the same as Liverpool - in eight previous meetings between the two teams.
Liverpool's record-breaking late show
Arne Slot's side have last season's brilliant performance in the league stage to live up to and will be hoping that they don't require another late, late showing to get them over the line.
That's because so far this season Liverpool have scored all of their Premier League winning goals in the last 10 minutes or later, something no team has ever managed before.
Whilst that shows a never say die attitude, it also hints at some of the issues facing the Dutchman this season.
In 2024/25, the Reds were imperious for the most part in the UCL, winning the league stage with the most points (21) and the most wins (seven).
Their only loss from their eight league games came on the final matchday, against PSV, when Slot was able to rotate his squad heavily due to the fact that Liverpool were already through.
Fortress Anfield
At Anfield in particular they'd become very difficult to play against, with even reigning champions, Real Madrid, losing 2-0. Ten goals scored at the famous old ground and only one conceded in those home games tells its own story.
Only against eventual winners Paris Saint-Germain did they succumb in the knockout stages, and it's easy to understand why Liverpool remain amongst the favourites to go all the way in 2025/26.
Particularly with talisman, Mo Salah, on song. The Egyptian King has scored more goals (44) and provided more assists (17) than any other Liverpool player in the premier European competition to date, and he showed against Burnley that the goalscoring fire still burns as brightly as ever.
There's nothing to suggest that he won't play a part on Wednesday, and in so doing he will leapfrog Steven Gerrard in the all-time Champions League appearance list for the club.
Currently level with the Anfield outfit's former captain on 73, he would have a chance of overhauling Jamie Carragher's 80 UCL appearances before the current season is finished.
Atletico's brilliant UCL opening game record
Though it's been a while since Atletico have got anywhere near the final, under Diego Simeone, the Spaniards have only lost one of their last 10 Champions League openers. What's more, the Argentinian has got the better of the Dutchman in both games where they've been in opposition to date.
In fact, Atletico under Simeone have kept a clean sheet in 42% of their Champions League matches (48 from 115).
It is worth pointing out that in the games against Slot's Feyenoord side, the Dutch giants did have more shots at goal (29 compared to 16), but weren't able to breach Atleti's famed defensive set-up enough times to get over the line.
We may see a similar story developing at Anfield during the course of the game, with the Rojiblancos content to sit back and soak up any Liverpool pressure, aiming to hit the hosts on the counter as and when the opportunities present themselves.
With Virgil van Dijk and Ibrahima Konate at the back for the Reds, the visitors will certainly have their work cut out to do precisely that; however, given that of the centre-back duos or trios with at least five starts in the Champions League last season, the Liverpool pair had the highest clean sheet percentage (71% - five in seven games).
Griezmann needs to shine
In normal time at Anfield, Liverpool have won three games against Atletico - including the last time the two teams met in 2021/22 - and drawn one.
They will have their own talisman, Antoine Griezmann, on hand to create chances that will hopefully be taken by Alexander Sorloth.
The French World Cup winner has either scored or assisted for 26% of Atleti’s Champions League goals (51/197), which is the highest percentage of any player in a team that have scored at least 100 goals in the competition.
Julian Alvarez will be a huge miss for the visitors, and he is joined on the sidelines by Alex Baena, Thiago Almada, and Jose Maria Gimenez.
Alvarez's international colleague, Alexis Mac Allister, may also miss out for the hosts along with Curtis Jones, and it remains to be seen if Slot is going to unleash Alexander Isak.
It's another fascinating European game in prospect, with a very real possibility of it turning into the unstoppable force against the immovable object.
