Federico Macheda scored the only goal of the game on 21 minutes, but Usuthu had enough more than chances to draw level, only to be let down by some wayward shooting.
United asserted their dominance in the opening exchanges though, aided in no small part by a very nervous home side.
They almost scored in the second minute when Dimitar Berbatov broke through a fired a shot that Tapuwa Kapini could only parry. However, Javier Hernandez could not put the rebound away.
Young right-back Robert Brady was next to test the defence after running onto Jesse Lingard’s pass, but a last-minute block denied him.
AmaZulu finally strung together some meaningful passes on 18 minutes, and it almost resulted in a goal. Tsweu Mokoro found some space down the right and squared to Goodman Dlamini, but he ballooned his effort over from the edge of the box.
Then, on 21 minutes, United finally got their goal. Federico Macheda ran onto a through-ball and fired a shot on goal which Kapini got a hand to, but could not prevent going over the line.
AmaZulu almost equalised straight away through Ayanda Dlamini, but goalkeeper Anders Lindegaard made a fine one-handed save low down.
Dlamini had another chance five minutes before the break, and again it was Ayanda Dlamini, but he dragged his shot wide when it was easier to score.
United almost doubled their lead just before the halftime whistle when Berbatov smashed a first-time volley from the edge of the area, but Kapini pulled off a flying save to deny the Bulgarian.
Berbatov continued where he left in the first half, forcing first Van Heerden to block his shot on the line, and then Kapini to save point-blank.
But that was as good as it got for United in the second half as AmaZulu took charge of the game.
Lindegaard was at his best to deny Ayanda Dlamini, while Kagiso Senamela hit a powerful drive straight at the goalie.
Bongani Mbele almost equalised with a header on the hour-mark but again Lindegaard was on hand to save the day, before Dlamini wasted yet another chance when he shot over from inside the box.
The game got scrappy as the substitutes came on, with United limited to long-range chances from Lingard and Javier Hernandez.
They almost added a goal in the dying minutes when substitute Davide Petrucci hit the bar, but that would have been unfair on AmaZulu, who dominated the second half, with Van Heerden and Senamela the two stand-out players.
AmaZulu starting XI: Tapuwa Kapini, Tsweu Mokoro, Mark, van Heerden, Carlington Nyadombo, Bukasa Kasonga, Ramson Zhuwawo, Bongani Mbele, Kagiso Senamela, Sifiso Vilakazi, Goodman Dlamini, Ayanda Dlamini
Manchester United starting XI: Anders Lindegaard, Frederic Vaseli, Scott Wootton, Rio Ferdinand, Robert Brady, Jesse Lingard, Paul Scholes, Michael Carrick, Federico Macheda, Dimitar Berbatov, Javier Hernandez
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