The 28-year-old United captain, who agreed a new pounds 10m-plus four-year deal with the treble-winners hours before kick-off, revived their defence of the Champions' League title with his fifth goal in nine games.
Further goals by Ole Gunnar Solskjaer, after 47 minutes, and Paul Scholes, after 68, sealed victory for United. They now go into the competition's winter break second in Group B, a point behind Fiorentina.
"It has been a very good day for Manchester United," said their manager Sir Alex Ferguson. "First, with the news of Roy Keane signing a new contract and then with the subsequent performance, particularly in the second half when I felt we reached our best form."
During that half United produced several passages of flowing football with David Beckham prominent. In front of the referee who sent him off at the World Cup, Kim Milton Nielsen, he underlined his candidacy for the European player of the year crown which is to be announced later this month.
Given the abuse he has overcome he would be a worthy winner but last night underlined the belief that Keane really deserves the award. Without his contribution Beckham and company would not be able to catch the eye and last night, after a slow start, he ran the midfield, ultimately eclipsing the dangerous Gaizka Mendieta as he broke up Valencia's attacks and started United's.
It was clearly nothing less than United had expected, for they had set the agenda by announcing his new deal, not before the match, but a few minutes after kick-off. The public responded and so, said Ferguson, did the players.
"I think it lifted them," he added. "They want the best players here and they all respect Roy Keane. They think he is a great player and they are all pleased."
"I'm glad it is all settled because I feared I would be forced to move to a foreign club," said Keane. "I've got to thank the gaffer for backing me and give credit to United for coming up with the improved offer."
Keane said the presence of Ferguson was one reason for his decision to stay and the manager responded: "I have a good relationship with him, he epitomises everything I believe a footballer should be - his determination, his will to win, his hunger. They are all qualities I can identify with."
Forty, fifty, sixty grand a week? Whatever Keane gets is excessive compared to nurses, Prime Ministers and most football supporters but there was not a word of criticism at Old Trafford last night. The money may be ridiculous but, in the context of the Champions' League, where every win can be worth millions, it is perfectly sane.
Not that Keane did much to justify it in the initial stages. A mis-kick in front of goal and a loose pass when a break was on were his first contributions. He looked as if the negotiations had drained him of energy.
Perhaps because of this Valencia were able to play their part in an open start with a first-minute Mendieta cross causing panic in the re- jigged United defence (Gary Neville was moved to the centre with Henning Berg dropped) before Raimond van der Gouw, with a double save from Francisco Farinos, calmed them.
As Keane found his feet United responded with a series of corners and, after 16 minutes, Solskjaer brought a save from Andres Palop after an elaborate free-kick.
Though Ryan Giggs went close in open play, his deflected shot looping just wide, dead-ball situations proved to be United's most fruitful avenue of attack. After 31 minutes Beckham, from 25 yards, struck the angle of the goal with a free-kick then, from another, United scored. Taken by Giggs it was cleared only as far as Gary Neville, his chip was nodded down by Solskjaer and Keane sweetly volleyed his fourth Champions' League goal of the season.
Two minutes after the break United doubled their lead. Beckham skipped down the right flank and crossed low and fast to the near post where Solskjaer, taking advantage of hesitancy by Mauricio Pellegrino, scored.
United relaxed and nearly paid for it as Valencia wasted a series of chances. Jocelyn Angloma at least had the excuse that Van der Gouw made a good save from his 20-yard shot but both Claudio Lopez and Oscar should have done better.
United, sensing the need to kill the game off, raised the tempo again and, from a Beckham free-kick, Scholes rose to head in. The rest of the match was an exhibition with Beckham, especially, revelling in the atmosphere. It was Keane, however, who was saluted by the United faithful at the end.
Manchester United (4-4-2): Van der Gouw; P Neville, Stam, G Neville, Irwin; Beckham, Keane, Scholes (Butt, 70), Giggs; Solskjaer, Cole (Yorke, 70). Substitutes not used: Culkin, Sheringham, Cruyff, Berg, Higginbotham.
Valencia (3-4-1-2): Palop; Bjorklund, Djukic, Pellegrino; Angloma, Milla, Farinos, Carboni; Mendieta; Claudio Lopez (Vlaovic, 85), Oscar (Sanchez, 67). Substitutes not used: Bartual, Camarasa, Soria Lopez, Fagiani, Cabezas.
Referee: K Nielsen (Denmark).
n Roy Keane's record contract was greeted warmly in the City. Manchester United's shares shot up 4.5p to 191.5p, a rise of more than two per cent.Reuse content