First-half goals from Aaron Mooy and Laurent Depoitre put the Terriers on their way to a famous victory at the John Smith's Stadium, which they managed to see through despite a late Marcus Rashford consolation.
After masterminding Huddersfield's return to the top flight last season, Wagner can now add a first Huddersfield triumph over the Red Devils since 1952 to his growing list of achievements.
Speaking to BBC Sport after the match, he said: "I said to the players that I wouldn't expect a result, but that I can believe in a result. That is why it so huge for us. It's a very proud moment, that we were able to beat Manchester United at home. In one game you can have a chance.
"If there is a chance, try to catch it. Today was our moment because we were at our best and maybe they weren't. It is one of the proudest moments in my career. It makes me very happy. I haven't thought about why Manchester United weren't at their best. They have played a lot of games and they had injury problems.
"It could be they are not at their freshest, but we didn't think about that. If this is our moment, we have to grab it, which is what the players did. Small Huddersfield have beaten Man United and it one of the proudest moments in my managerial career.
"It's another chapter in the fairytale we started nearly two years ago. It has shown everything is possible in football. Today was our moment. It makes everyone very happy and very proud."