Manchester United's air of optimism was punctured as Alex Iwobi's 97th minute winner handed Fulham their first win at Old Trafford since 2003, while Manchester City edged past Bournemouth 1-0 to close the gap on leaders Liverpool to one point.
The completion of Jim Ratcliffe's minority stake in United this week and a spell of good form had brought hope of a fresh start for the Red Devils.
United had won their previous four Premier League games to rekindle hope of qualifying for next season's Champions League, but a 2-1 defeat leaves them eight points adrift of Villa.
Ratcliffe revealed his ambition to topple Manchester City and Liverpool at the top of the English game within three years.
But the work that lies ahead of the British billionaire on and off the field was exposed as Fulham dominated a ragged United for long spells.
Fulham finally took one of their chances midway through the second half when Calvin Bassey lashed home his first goal for the Cottagers from a corner.
United looked to have snatched a point against the run of play late on when Harry Maguire tapped in after Bernd Leno spilled Bruno Fernandes' effort.
But there was another twist in the tale as Fulham secured their first away win since the opening day of the season.
Adama Traore left Maguire trailing in his wake before teeing up Iwobi to curl inside Andre Onana's near post.
"The players deserved it, clearly the best team won the game," said Fulham boss Marco Silva.
Foden saves City
City were again far from their flowing best but, just like in a 1-0 victory over Brentford in midweek, did enough to keep their title challenge on track.
The in-form Phil Foden scored the only goal at the Vitality Stadium as the England international stroked into an empty net for his 16th goal of the season after Neto parried Erling Haaland's initial effort.
At the other end, Ederson was required to save City from dropping two costly points when he kept out Dominic Solanke's header on the line by the finest of margins.
And former City forward Enes Unal was inches away from an equaliser when his header shaved the post in stoppage time.
Aston Villa opened up a five-point lead over Tottenham in the battle for a top-four finish with a 4-2 win over Nottingham Forest.
Unai Emery's men were coasting towards a first home win of 2024 as they led 3-0 inside 39 minutes.
Ollie Watkins tapped in Leon Bailey's cross after just four minutes before Douglas Luiz struck twice.
Forest remain just four points above the relegation zone and reacted too late to help their survival hopes.
Moussa Niakhate pulled a goal back deep into first-half stoppage time before Morgan Gibbs-White's delightful dink cut Forest's deficit to one just three minutes into the second period.
However, Villa quickly restored their two-goal cushion when Leon Bailey tapped in after Watkins' initial effort was saved.
Glasner's dream start
Oliver Glasner got off to a dream start as Crystal Palace manager with a 3-0 win over 10-man Burnley.
Former Eintracht Frankfurt boss Glasner could not have wished for a kinder fixture to start against a Burnley side seemingly destined for an immediate return to the Championship.
Any hope of a first win this year for Vincent Kompany's men disappeared with a first-half red card for Josh Brownhill.
Chris Richards opened the floodgates 22 minutes from time as Palace moved eight points clear of the relegation zone.
Jordan Ayew made it 2-0 before Jean Philppe-Mateta's penalty rounded off the scoring.
Everton were denied a huge win in their battle to beat the drop by Lewis Dunk's 95th minute equaliser for Brighton in a 1-1 draw at the Amex.
Jarrad Branthwaite's thumping finish on 73 minutes opened the scoring before Brighton were reduced to 10 men when Billy Gilmour saw red.
A point edges Sean Dyche's men just one point clear of the relegation zone.
Third-placed Arsenal host Newcastle later on Saturday aiming to move back to within two points of Liverpool.
