Danny Murphy ended Liverpool's penalty curse to boost their hopes of qualifying for the Champions League.
Murphy scored the winner from the spot after 63 minutes following a reckless challenge by Gary Neville on Liverpool captain Steven Gerrard.
He took responsibility after misses from Michael Owen and Gerrard.
Murphy's goal settled a cagey encounter which produced few clear chances, although United's Ryan Giggs hit the post in the second half.
It was the third time Murphy has scored the deciding goal at Old Trafford under boss Gerard Houllier, who saw the pressure on him relieved slightly by the victory.
Liverpool's triumph - their third at Old Trafford in four years - ended the very slim mathematical chance United still had of winning the title.
63 mins: Danny Murphy scores from the penalty spot
United were without striker Ruud van Nistelrooy, who suffered a slight thigh strain in training, while Liverpool recalled Steve Finnan and Danny Murphy.
Tim Howard was also recalled in place of Roy Carroll, and he was forced to smother a loose ball as Murphy closed in.
Liverpool were solid, and might even have snatched the lead had Michael Owen been able to find a team-mate as a cross flashed across the six-yard area.
Ronaldo was stretching Liverpool and created half-chances for Louis Saha and Darren Fletcher.
But the Portuguese youngster's frustration got the better of him when he was booked by Mike Riley for throwing the ball into the stand after failing to get a free-kick.
Giggs almost broke the deadlock as the interval approached, firing a powerful volley narrowly wide after Saha flicked on Howard's goal-kick.
The second half opened in the same cautious fashion, but Liverpool made a change on the hour, sending on Vladimir Smicer for Finnan.
And three minutes later Liverpool were ahead when Neville hauled down Gerrard.
Murphy stepped up following failures this season from Michael Owen and Gerrard, and shot high past Howard.
Giggs almost equalised as United pressed, hitting the inside of the post and substitute Ole Gunnar Solskjaer missed a glorious chance seconds later.
And Dudek then saved well from Saha with four minutes left as the pressure increased.
But Liverpool held on for a vital victory.
Man Utd: Howard, Gary Neville, Brown, Silvestre,
O'Shea (Solskjaer 65), Fletcher, Keane,
Phil Neville (Bellion 82), Ronaldo, Saha, Giggs.
Subs Not Used: Carroll, Butt, Djemba-Djemba.
Booked: Ronaldo, Silvestre.
Liverpool: Dudek, Finnan (Smicer 60), Henchoz, Hyypia,
Carragher, Murphy, Gerrard, Hamann, Riise, Owen (Heskey 84),
Kewell (Cheyrou 81).
Subs Not Used: Baros, Luzi Bernardi.
Referee: M Riley (W Yorkshire).