Van Gaal: I want to kiss man-of-the-match Memphis
The hosts went behind after just eight minutes when Michael Carrick turned Victor Vazquez's free kick into his own net, before Depay equalised five minutes later.
The Dutchman curled in a second just before half-time then set up Marouane Fellaini's third at the death, admitting later he was frustrated not to score a hat-trick, and Van Gaal heaped praise on the 21-year-old.
"I want to kiss him tonight because when you score two goals and have an assist then normally in the world you are the hero," he told reporters.
Van Gaal admitted relief at securing a two-goal lead ahead of next week's play-off second leg, but warned that the tie is by no means settled before heading to Belgium in eight days' time.
He added: "Yes it is a difficult ground, and it is not a simple opponent. I have read in the papers in England that it is simple and it is a walkover, but it isn't like that.
"Every team that comes, such as Brugge against Panathinaikos, they won 3-0 [in the previous round]. It is still a game, but because of the last goal we now have more confidence."
Wayne Rooney again struggled in attack despite Depay's lively performance in support, but Van Gaal dismissed concerns over his striker's ongoing goal drought, adding: "He had a shot on goal [in the first half] so I'm happy."
Michael Carrick was replaced at half-time, but his manager insisted the player's earlier error played no part in his decision, with Bastian Schweinsteiger in need of first-team minutes following his summer arrival.
"It was a tactic switch. I have to also build up Schweinsteiger and that is why I changed Michael for Schweinsteiger," he said
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