All three played the full 90 minutes as the second string ran out 3-1 winners.
With a seven-day break between competitive games, manager Sir Alex Ferguson spoke of the Moss Lane game as a perfect opportunity for some to gain further match fitness ahead of a hectic run-in.
"It’s the first time in quite a while that we’ve got a break and it can be useful," Sir Alex told the club’s official website.
"I think one or two players probably need a break but not the likes of Tom Cleverley, who is recently back from injury and is probably going to relish a game in midweek.Goals from youngsters Will Keane and Jesse Lingard put United 2-0 up inside 11 minutes, only for Daniel Johnson to peg them back just after the break.
Smalling put the game beyond doubt on the hour mark to keep his side top of the 'Premier Reserve League - North', level on points with Sunderland having played two games less.
Manchester United Reserves (4-4-2): Johnstone; De Laet, Smalling, Jones, Fabio; Pogba (Tunnicliffe 61), James (M Keane 72), Cleverley, Petrucci, Lingard (Vermijl 78); W Keane. Subs not used: Coll, Fryers.