The Mexican came off the bench at half-time to score two goals and force another as the Red Devils strengthened their grip on top spot with a dramatic victory at Villa Park
Andreas Weimann completed sweeping counterattacking moves either side of half-time to send Paul Lambert's side into a shock two-goal lead.
But Chicharito, who had replaced Ashley Young at the break, made all the difference. The Mexican pulled United back into the game after 58 minutes before another of his shots deflected off Ron Vlaar to level the score.
And the clinical striker finally made United's pressure pay when he headed home Robin van Persie's free-kick in the final minutes at Villa Park.
Enda Stevens made his first Premier League start at left-back for the hosts in place of Joe Bennett, who was injured in the 1-0 victory over Sunderland at the Stadium of Light.
Sir Alex Ferguson made two changes to the side that beat Arsenal 2-1 the previous weekend. Chris Smalling made his league return in defence in place of Jonny Evans, who had a groin injury, while Tom Cleverley dropped to the bench to be replaced by Paul Scholes in central midfield.
Former Villan Young was involved and shot narrowly wide as United controlled the early exchanges. However, Weimann was left ruing his own indecision when he failed to pick out either Christian Benteke or Stephen Ireland at the end of a three-on-two counterattack.
For most of the first half, the possession statistics showed United enjoying around 70 per cent of the ball but Villa, led by Vlaar in central defence, continued to stand up to the test and the visitors' frustration grew.
On the stroke of half-time, Lambert's team made their excellent rearguard resistance count. Agbonlahor initiated a break down the left flank that was continued by Benteke. The Belgian showed tremendous pace and power to shake off the challenge of Chris Smalling before rolling the ball into the path of Weimann, who slammed a shot from 18 yards into the roof of the net.
Ferguson did not hesitate to make a change. Young, who had faded as the half wore on, was withdrawn at the break for Chicharito. The sloppy play which had plagued them - for which Scholes was unusually culpable - persisted, though, into the second 45 minutes.
Villa were not as devastatingly quick when they moved upfield after the veteran had misplaced a pass as they had been for their opening goal, but again it was Benteke that played a significant role in exposing the United defence. His dummy created the space in which Ireland was able to pick out Agbonlahor, whose low cross from the left was swept home by Weimann.
Scholes went some way to making amends by playing the pass that brought United back into the game just before the hour mark. Chicharito did superbly to control the midfielder's chipped ball and shake off Ciaran Clark before steering a low finish through the legs of Guzan.
Within five minutes, United were level. Agbonlahor failed to track the run of Rafael on the right flank and when the Brazilian crossed to the far post, Chicharito was on hand to pounce with the help of a deflection off Vlaar.
Weimann almost had a hat-trick when he was denied by De Gea from close range but for the majority of the final 20 minutes, Benteke was the only Villa player not stationed behind the ball. When Van Persie struck the crossbar twice in quick succession, the signs were ominous.
And just as Villa seemed to have weathered the worst of the storm, Chicharito headed home from the Dutchman's inswinging free-kick to strengthen the Red Devils' grip on top spot in dramatic style.