The Belgium international, a free summer signing from Borussia Dortmund, will experience a Madrid derby for the first time. But also, despite his long and successful career, it will be the 33 year-old's first time facing Real Madrid in a competitive game.
Witsel and Atletico go into the derby as underdogs as they face a Real Madrid boasting a 100 per cent record so far this season. Carlo Ancelotti's side are the only team in Europe's top five leagues with a perfect record - both domestically and in Europe - this campaign and they lead Barcelona at the top of the standings by two points after five games.
However, Witsel says he and his teammates will be motivated to pull off an upset on Sunday. The veteran revealing Atleti's players have been looking forward to the fixture since the start of the season.
"One of the reasons we are in football is to play in games like this," he continued.
"From a young age, you dream of being a professional footballer, and playing in a game like this."
Both teams have their injury problems ahead of Sunday, with Real Madrid hopeful of Karim Benzema overcoming a nagging knee strain. Atletico, meanwhile, will miss former Real Madrid fullback Sergio Reguilon.
There will also be late fitness tests for Atletico goalkeeper Jan Oblak (back), central defensive pair Stefan Savic (hamstring) and Jose Maria Gimenez (back) and midfielder Thomas Lemar (muscle problem).
For Witsel, if Atletico can play to their potential, they will have every chance of upsetting the defending La Liga title holders.
He adds, "They [Real Madrid] have a really good squad with a lot of stars. Benzema is in extraordinary form. He's always been a great player, and maybe this season he'll get the Ballon d'Or.
"We've got a very strong squad. Physically, we are in great shape, so it's up to us to play to our potential and give it all we've got."
Watch Axel Witsel preview El Derbi Madrileno below: