Gabriel Agbonlahor's header gave Villa their first league win at Old Trafford since 1983 and provided a welcome boost to Chelsea who had earlier been held 3-3 at home by Everton on a day of surprise results and a breathtaking goal-of-the-season entry by Wigan Athletic defender Maynor Figueroa.
Chelsea's recent defensive fragility continued as they dropped their first home points of the season to extend their run of games without a win to four - a sequence which has seen Carlo Ancelotti's side leak 10 goals.
Tottenham Hotspur, who began the day in fourth place, were beaten 1-0 at home by Wolverhampton Wanderers, their first loss to the Midlands side at White Hart Lane since 1973.
Top-four hopefuls Manchester City could only draw 3-3 at Bolton with Carlos Tevez bagging two goals for City, who had Craig Bellamy sent off but came from behind three times.
Villa's first win of any sort against United for 10 years was fully deserved and means that Martin O'Neill's side have beaten United and Chelsea already this season.
United were lacking invention and striker Michael Owen, left out despite scoring a hat-trick against Wolfsburg in the Champions League, had few chances when he came on after the break as Villa clung on after Agbonlahor's 21st minute effort.
"They worked their socks off and for that I give them full credit," United manager Alex Ferguson, who was infuriated by the lack of stoppage time added on, said after his side's fourth league defeat of the season.
The closest United came to an equaliser was when Wayne Rooney's shot rebounded off the underside of the crossbar.
While United's attack malfunctioned, Chelsea's problems stemmed from some comedy defending, although Ancelotti was not unduly concerned by the present insecurity at the back.
"Against APOEL Nicosia (a 2-2 draw in the Champions League on Tuesday) I was angry but not today," Ancelotti, whose side had not conceded a home league goal since the opening day of the season, told reporters.
"We played with intensity and good concentration for 90 minutes and created lots of chances. Sometimes it happens that you draw but when you play like we did you deserve to win."
His side's troubles began as keeper Petr Cech inadvertently gave Everton an early lead when an effort on goal by Louis Saha rebounded off a post and into the net off his body.
Chelsea responded and were ahead by the 23rd minute with goals from Nicolas Anelka and Didier Drogba. Another lapse at the back allowed Yakubu to make it 2-2 just before halftime.
Drogba's volley, his 13th league goal of the season, soon after the restart put Chelsea back in front but the Ivory Coast striker had a hand in Saha's equaliser when his clearing header unluckily rebounded off the Frenchman and past Cech.
Six of the day's fixtures ended in draws, the most entertaining of which was at the Brittania Stadium where fans witnessed Figueroa's outstanding free kick from inside his own half for Wigan.
Sadly for the Honduran it did not prove to be the winner as Stoke levelled to make it 2-2.
