Red Devils run out dominant winners as fine goals from Rooney and Berbatov add gloss to a fine performance with United finding itself three up at halftime.
United took a 3-0 lead to halftime thanks to and early goal from Welbeck followed by a header from Nani and a deflected shot from Giggs, but really turned on the style with the final two goals as Rooney and Berbatov finished with aplomb.
Manchester United made one change to the side that defeated QPR in West London on Sunday with Anders Lindegaard coming in to replace David de Gea.
Elsewhere, Wayne Rooney astonishingly became the youngest ever player in the Premier League to make 300 appearances at the age of 26 years and 58 days, eclipsing Gareth Barry's record of 26 years and 247 days set in 2007.
Fulham was unchanged from its 2-0 victory over Bolton on Saturday with Martin Jol keeping his faith in Andrew Johnson as the lone striker up front.
United was almost forced into an early change when Phil Jones, deployed at right back, challenged with Clint Dempsey in the air and took a knock to the head. He was off the pitch for some time before he eventually re-joined the action, and almost as soon as he did the away side was in the lead.
Patrice Evra fed the ball to Nani on the halfway line, and the Portuguese winger was allowed to run unchallenged to the byline before sending in a pass to an unmarked Danny Welbeck to slot home.
Fulham almost got back level after 20 minutes as Bryan Ruiz played a neat one-two with Dempsey on the edge of the area before bearing down on goal, only to be thwarted by a fantastic last-ditch tackle from Phil Jones who sent the ball out for a corner.
It was to be the young defender’s last action of the match as he was substituted straight afterwards, though it wasn’t clear whether this was due to the block on Ruiz or if he was still suffering the effects of the clash with Dempsey earlier in the game.
It didn’t seem to phase United, which brought on Ashley Young in his place, and doubled the lead not long after.
A series of corners came United’s way, and the club employed a short corner routine, with the final one resulting in a goal for Nani, who glanced a fantastically whipped ball from Ryan Giggs into the far corner.
United was extremely dominant, and it began to tell as Nani and Valencia were combining fantastically down the right wing, and it was this pairing that set up the third goal for United before halftime.
After Valencia intercepted a cross-field pass, United broke with speed and Nani found Giggs on the edge of the box where he attempted to slot home, with Senderos sending his shot looping in over the top of the unfortunate Stockdale.
The home side left the field to a chorus of boos from the fans, and it would take something very special to come back from such a heavy deficit against the reigning champion.
Fulham actually started the second half quite brightly, forcing three good efforts in the opening 10 minutes.
Anders Lindegaard was forced into his first real stop of the match as he got down well to prevent a header from Dempsey creeping over the line, and a minute later Moussa Dembele went close. John Arne Riise then saw a free kick fade just wide after Danny Murphy’s lay off.
Fulham was undoubtedly coming into the game, but faced a good blockade in the United defense which stayed strong until the end.
In the final few minutes, Wayne Rooney capped his landmark performance with a fine goal, as he was left in too much space and drove a fantastic effort in off the post that left Stockdale with no chance.
Minutes later, substitute Dimitar Berbatov made it five, back-heeling the ball into the far corner after a good break and cross from Valencia.