Rafa Benitez's men produced an excellent second half display with goals from Juan Mata and Ramires equaling Wayne Rooney and Chicharito's early finishes.
The first half was dominated by the Red Devils as Chelsea endured a torrid first 10 minutes, with Chicharito opening the scoring with a header, before Rooney extended the lead with a fortuitous free kick.
It was truly a tale of two halves though as Chelsea controlled the second period, eventually getting its just rewards with a stunning effort from Eden Hazard and a smart finish from Ramires The Blues were unable to complete the comeback despite some late pressure.
Sir Alex Ferguson chose to retain the bulk of the side that fell to a disappointing Champions League exit on Tuesday, though he made four changes as Jonny Evans, Shinji Kagawa, Wayne Rooney and Chicharito came in, at the expense of Nemanja Vidic, Danny Welbeck, Ryan Giggs and Robin van Persie.
Rafa Benitez, meanwhile, made wholesale changes as only Petr Cech, David Luiz, Oscar and Frank Lampard remain from the side that fell to a 1-0 defeat against Steaua Bucharest on Thursday, with John Terry, Eden Hazard and Fernando Torres among those notably excluded.
It took just four minutes for the deadlock to be broken and it came virtue of a Chicharito header as the home side took an early lead. Michael Carrick played a magnificent through ball into the diminutive Mexican's path and the striker took it early on his head, surprising the advancing Petr Cech by looping the ball deftly over the goalkeeper and into the far corner.
With Chelsea still shell shocked, the Red Devils manage to extend their lead mere minutes later. After Victor Moses felled Nani out wide following a typically rapid counterattack, Rooney stepped up to swing in the free kick. Despite seemingly attempting to find a teammate with the cross, no one managed to get a touch on it and it found its way past Cech into the far corner, leaving the Blues chasing a two-goal deficit with just 10 minutes gone.
Chelsea continued to struggle as the half wore. Both Chicharito and Rooney spurned chances to extend the lead further, with the away side's opportunities in the first period limited to half chances. Moses should have done better after cutting inside in the area, instead slicing his shot well wide, while David De Gea was called into action after a dangerous Juan Mata cross.
Though Manchester United's impetus continued into the second half, Chelsea began to come into the game and it took 15 minutes and a moment of brilliance for the pressure to show. Hazard, after receiving the ball to the left of the penalty area, took one step inside and curled it into the far corner with a great deal of finesse, leaving De Gea with no chance.
With 20 minutes remaining, United attempted to put itself out of distance with a third goal and, in doing so, committed too many men forward and Ramires was the man that made United pay.
Luiz intercepted an attack on the edge of his area and set the counterattack in motion. Eventually it ended with Ramires bearing down on goal and, after the Brazilian turned into his left, he stroked it into the opposite corner, leveling the game.
The Red Devils started to exert some pressure with 15 minutes remaining as substitute Robin van Persie had his shot blocked, before Carrick's effort from the ensuing melee suffered the same fate.
Chelsea had the better of the last 10 minutes but was unable to capitalize on the pressure as Mata had the best chance to win the game. De Gea was on hand to produce an excellent save from his side footed effort, meaning that a replay beckons for both of these sides.