كتب : Hatem Maher
Jermaine Beckford scored the memorable winner after 19 minutes to send the visiting fans into raptures.
He latched onto a long ball, outpaced central defender Wes Brown and fired home past United keeper Tomas Kuszczak.
"The preparation for the game was very good, but I’m shocked by the performance," United coach Alex Ferguson told MUTV.
"We didn't start right and Leeds did start right. They got their goal and had something to hold onto.
"They fought like tigers, and we expect that with any team coming to Old Trafford for an FA Cup tie. It’s a disappointment."
The Red Devils, who won the FA Cup 11 times, lost despite relying on several regular players, including strike duo Wayne Rooney and Dimitar Berbatov.
Ryan Giggs, Antonio Valencia and Michael Owen were also introduced in the second half but they failed to spare the team's blushes.
It is the first time United lose in the third round of the FA Cup and taste defeat against a lower-division side since Ferguson took over in 1986.
Losing against Leeds, once fierce rivals, is their biggest upset since they were dumped out by Bournemouth in 1984.