Macheda's goal in the 76th minute kept United top of the standings and a point ahead of Liverpool, which eased to a 4-0 victory over Blackburn. Last weekend, the 17-year-old Italian scored a late winner on his debut to give United a 3-2 victory over Aston Villa.
"He looks like a great goal scorer and hopefully there's more to come," said Paul Scholes, who is exactly twice Macheda's age. "He's a young lad and I'm sure the others will help to keep his feet on the ground."
Scholes had put United ahead after 19 minutes, but the midfielder's header was cancelled out by Kenwyne Jones in the 55th.
Fernando Torres scored twice to help Liverpool to its fifth straight league win. Emotions were running high at Anfield before kickoff when a minute's silence was held to mark the 20th anniversary of the Hillsborough stadium disaster, which claimed the lives of 96 Liverpool fans.
United, which still has a game in hand, tops the league with 71 points. Liverpool is second with 70 and Chelsea, which edged Bolton 4-3 after leading 4-0, is third on 67.
Buoyed by Liverpool's lunchtime win, manager Rafa Benitez claimed the Red Devils were "under pressure" and their manager Alex Ferguson "nervous."
Had it not been for Macheda's winner at the Stadium of Light, Benitez's side would be top.
Seconds after replacing striker Dimitar Berbatov, United's most expensive player, Macheda steered home a low shot by Michael Carrick that was heading wide.
"As soon as the ball came to him he put his foot on it and that's the instinct of a striker," Ferguson said. "We're very hopeful for the boy - he's got a great eye for goal and a tremendous physique."
United's early domination was capped by Wayne Rooney cutting inside and crossing for the unmarked Scholes to glance a header past stranded goalkeeper Craig Gordon and into the top corner.
After that Sunderland squandered a string of chances to equalize before Jones scored when United goalkeeper Ben Foster failed to claim Teemu Tainio's cross and the striker fired into the empty net.
"I thought Ben should have done better with the goal," Ferguson said. "We rode our luck at bit and we got a bit sloppy at times."
Liverpool needed only five minutes to take the lead at Anfield. Jamie Carragher sent a lofted pass from the halfway line which Torres chested down before swiveling and hooking a superb volley into the far corner.
Torres beat Blackburn's Chris Samba in the air to head home Xabi Alonso's cross in the 33rd minute, Daniel Agger blasted a swerving shot past Paul Robinson in the 83rd and David Ngog nodded in Lucas Leiva's header across the face of goal in the 90th.
Midfielder Steven Gerrard, who is struggling with a groin problem, remained on the bench and could feature at Chelsea in the second leg of their Champions League quarterfinal as Liverpool looks to recover a 3-1 deficit.
"The last game wasn't good but we've done our job today," Torres said. "We have confidence after this result to go to Stamford Bridge."
Chelsea was 4-0 up after 63 minutes thanks to two goals from Didier Drogba, a penalty converted by Frank Lampard and Michael Ballack's first league goal of the season.
But soon after coach Guus Hiddink replaced Drogba with Nicolas Anelka and Lampard with Deco in the 65th minute, Bolton scored three times in 11 minutes through Andy O'Brien, Chris Basham and Matt Taylor. Gary Cahill was only denied a stoppage time equalizer when Deco cleared off the line.
Arsenal went nine points clear of Aston Villa in the fourth Champions League spot after coming from behind to win 4-1 win at Wigan.
After Mido's early goal, Arsenal stormed back after the break with goals from Theo Walcott, Mikael Silvestre, Andrei Arshavin and Alex Song. Aston Villa hosts Everton on Sunday, when Fulham is at Manchester City.
At the other end of the table, Middlesbrough remains in the relegation zone on 30 points despite beating Hull 3-1.
Newcastle, also with 30 points, trails Middlesbrough on goal difference after Alan Shearer's second match in charge ended in a 1-1 draw at Stoke.
The defeat for Hull left the club four points above the drop zone - along with Portsmouth, which drew 2-2 against bottom-place West Bromwich Albion, which has 25 points.
Tottenham beat West Ham 1-0 to boost its bid for European qualification.
