Wednesday's clash will see Luis Suarez meet United for the tenth time, but his first meeting, in March 2011, was the most iconic, despite the fact he didn't score a single goal.
It may be hard to imagine now with the current state of affairs, but United used to have one of Europe's toughest defences under legendary manager Sir Alex Ferguson.
The backline was impenetrable for much of his trophy-laden era, but was once taught a lesson by Suarez who was sampling the United vs Liverpool rivalry for the first time.
Suarez had already thrilled fans with a brilliant goal on his debut against Stoke, but he stepped it up a level at Old Trafford in his fourth game for The Reds.
Collecting the ball from a wildly out of position Sotirios Kyrgiakos after a cleared set piece, Suarez put the ball through Rafael da Silva's legs before eyeing up his next obstacle.
The Uruguayan then flew past an on-rushing Michael Carrick with a deadly touch, before leaving Wes Brown on the floor with a beautiful jink between his feet.
All that was left was Edwin van der Sar in the United goal, and the finish was there with Suarez stabbing the ball past the giant keeper at the tightest of angles.
With one of the greatest efforts of Suarez' career rolling along the goalline for its resting place in the side netting, out of nowhere came Dirk Kuyt to stab it home.
Suarez, the ultimate competitor, didn't seem too bothered as he ran off in celebration with his teammate, but little did he know he'd set Kuyt up for a headline-making hat-trick.
The Dutchman later nodded in from a horrendous Luis Nani clearance, and was again there to gobble up Suarez' seconds when Van der Sar spilled a free kick into his path.
The distance of Kuyt's three goals amounted to barely six yards, but as he later confirmed, he wouldn't change anything about the first one.
"For me, it was one of Luis' greatest goals but it just had my name on it," he said.
"I would love to give the goal to him but at the end of the day I wouldn't have scored a hat-trick against Man United.
"Even if I could turn back time, I would still probably score, because I know now that I'd score a hat-trick at the end of the day.
"At that moment, I wasn't sure if someone was behind me, I wasn't sure if the ball would go over the line.
"I would never forgive myself if I just put my hands up in the air, leave the ball for Suarez to have the goal and somebody just cleared it before the ball went over the line.
"I was never a player who stole goals and I had a very good relationship with Luis.
"So it's a difficult one. Suarez has got enough goals, enough silverware, so I don't think he blames me!"
Now Suarez will be hoping to dampen the mood at United, who come into the last 16 leg off the back of a thrilling win against Leeds. Atletic, though, like United, are struggling to find a way into the top four after a summer of heavy investment, made even worse by the fact they're reigning LaLiga champions.