United arrived in the capital minus their inspirational Irishman and started the match with their 3,000 travelling supports chanting his name.
But the chants of "Keano" were soon replaced by that of Ruud van Nistelrooy after the Dutchman's brace earned them all three points.
He should have put United in front in only the eighth minute when he sprang the offside trap.
The striker rounded keeper Stephan Andersen but saw his shot cleared off the line by Hermann Hreidarsson.
Wayne Rooney then fired a 12-yard shot over the bar after Wes Brown had laid the ball off to the England international striker.
Darren Bent had both of Charlton's best chances to opening the scoring. He first raced on to a long pass before producing a tame shot that was easily saved by Edwin Van der Sar.
Bent then made a real hash of a golden opportunity in the 34th minute, blasting his shot wide of the post after Talal El Karkouri's free-kick had struck the United wall.
As the "Keano" chants continued, it was fitting that the man trying to replace him, Alan Smith, should put the visitors in front.
Rooney surged into the box before crossing for Darren Fletcher. He in turn laid the ball back for Smith, who finished the move with a neat side-footed shot that flew into the bottom left-hand corner of the net.
Andersen was then called into action when he produced a stunning save to stop van Nistelrooy adding to United's lead. The Danish keeper tipped his blistering 20-yard shot over the bar.
After the restart Dennis Rommedahl was unlucky to see his shot from seven yards deflected over the bar.
Rooney proved to be a real handful for Charlton's defence and, in the 57th minute, he almost tore them apart. He danced his way into the box but saw his left-footed shot sail narrowly wide.
Charlton clawed their way back into the game against the run of play when Darren Ambrose levelled the scores in the 65th minute.
The England Under-21 winger received the ball from Bent and raced forward before curling his shot past Van der Sar from 25 yards.
Not to be upstaged, Rooney brought more of his magic to the game as United restored their lead.
He showed great determination to dispossess El Karkouri before producing a cheeky lob for van Nistelrooy at the far post.
The striker kept his composure and his shot on the turn beat Andersen for his 11th goal of the season in all competitions.
Van Nistelrooy then added United's third in spectacular fashion. He dispossessed Luke Young before unleashing a stunning strike from the edge of the box that gave Andersen little chance.
Charlton had chances at the death but could not find a way past Van der Sar as they were left still looking for their first win over United since 1989.
MAN OF THE MATCH: Ruud van Nistelrooy (Manchester United) - The Dutch striker was back to his clinical best, scoring two goals and proving to be a handful to the Addicks defence throughout.