Villa had gone 24 games against the Reds in any competition without a win, but the way their players celebrated at the end suggested they know they are not far away from breaking into that elite group of four clubs at the top of the Premier League.
Villa hassled United from the start. They never let them settle and capitalised on some poor defending for the only goal of the game after 21 minutes.
Standing a few feet short of the left corner of the United box, Agbonlahor held off a challenge from Nemanja Vidic to lay the ball back to Ashley Young on the wing.
Young looked up and produced a perfect measured cross as Agbonlahor continued his run in between Vidic and Wes Brown to meet the ball and plant his near-post header into the net from six yards.
United pressed forward and few people would have thought that would have been the end of the scoring.
Ryan Giggs and Wayne Rooney missed chances, while Rooney was rightly booked for diving after going down in the Villa box after brushing Luke Young.
Rooney was unlucky not to equalise from an exquisite piece of skill on the half hour.
Patrice Evra found the England man on the left side of the six-yard box. His clever drag-back left Carlos Cuellar for dead and Rooney lashed in a shot which crashed back into play off the underside of the bar.
United went for broke after the break when both Michael Owen and Dimitar Berbatov were brought on to give Rooney much needed support up front.
As time went on the signs were there that United would make one of their late great escapes.
But even when the Reds managed to get past the Villa defenders, they found their old nemesis Brad Friedel in superb form in the Villa goal.
With four minutes left, Berbatov produced a glorious bit of skill to glide forward and power in a shot from just inside the Villa penalty area which Friedel brilliantly turned behind.
Villa's win takes them to third place in the table and with victories against United, Chelsea and Liverpool, suggests they could finally be there to stay.