The £19million Dutchman scored twice in two minutes on his debut to secure a winning start for Sir Alex Ferguson in his last season as manager of Manchester United.
His strikes and one from David Beckham - direct from a free-kick, it hardly needs to be said - snuffed out two goals of exceptional quality from Fulham's brightest young star Louis Saha.
The result, however, showed just how far Fulham have come in a short space of time. Three years ago, the Cottagers opened their league campaign in the less than glamorous surroundings of Macclesfield's Moss Rose ground.
That their first fixture of the 2001-2 season should have been 15 miles further away at Old Trafford shows just what the deep coffers of chairman Mohamed Al Fayed and managerial skills of Jean Tigana have achieved.
This just the first rung on the Premiership ladder, but just to be facing the likes of Juan Sebastian Veron and van Nistelrooy must be a delight to the fans of a club which had played their last game in the top flight 31 years ago.
Fulham's sense of disbelief must have turned to incredulity when they took the lead four minutes into a game which was thrilling from the first whistle to the last.
Sean Davis, the promising 21-year-old midfielder who has now played for Fulham in all four divisions, lofted an accurate, but hopeful long pass which picked out Saha's run through the defence.
Saha, scorer of 32 goals last season, held off Gary Neville and brought down the ball with exquisite skill before deftly lobbing the stranded Fabien Barthez.
Beckham, confined to the right wing again despite Roy Keane's absence due to suspension - Phil Neville was assigned the holding role in midfield by Ferguson - struck the wall from a free-kick before Jaap Stam did enough to put off Saha when he seemed certain to score again.
Dutch keeper Edwin van der Sar, signed from Juventus for £7million in the summer, brilliantly kept out Beckham's curling effort from long range in the 14th minute, and had the woodwork to thank shortly afterwards.
Giggs' dazzling run saw the Welshman surge past three full-blooded attempts to stop him and from his cross United should have scored.
Van Nistelrooy swung at the ball and missed and then Paul Scholes hammered a first-time effort against the bar.
But it was not all United and Barthez was forced into a diving save after 25 minutes to parry Saha's forceful header from Steve Finnan's cross.
After less than 35 minutes, Ferguson effectively conceded that his policy of playing Scholes as a support striker to van Nistelrooy was not working when he brought on Andy Cole in place of Phil Neville.
Within seconds, United had equalised, though that had nothing to do with the substitution and everything to do with a controversial refereeing decision and Beckham's brilliance at set-pieces.
Another weaving Giggs run was ended by Finnan 25 yards out, with an apparently exceptional tackle. Referee Peter Jones, however, thought otherwise and awarded United a free-kick, much to the chagrin of the Fulham players.
Beckham waited for Cole and Neville to exchange places and then curled in a free-kick which rattled the underside of the crossbar on its way into the net.
Fulham had another glorious chance to take the lead again when Hayles raced through onto Saha's pass, but Barthez blocked his shot with his feet.
United too had a near miss, when Scholes, back in customary position in central midfield, hammered in a drive which van der Sar saw late and was perhaps fortunate to deflect wide with his body.
Less than three minutes into the second half and Saha stunned Old Trafford for the second time.
The long-legged 22-year-old Frenchman possesses frightening pace and when he burst onto Steed Malbranque's through-ball - once more leaving Neville trailing - the outcome seemed inevitable.
And so it was as Saha slotted the ball to Barthez's right.
United then completely changed the course of the match, with van Nistelrooy pouncing to score two poachers' goals in the 52nd and 54th minutes.
Ferguson's side had looked far more threatening with Cole playing alongside the Dutchman, and it was the substitute who manufactured the first, van Nistelrooy reaching his pass a second before his compatriot van der Sar to flick the ball in.
In United's next attack the striker seized on some dithering in defence by Bjarne Goldbaek to put the home side ahead from close range.
With 19 minutes remaining, Cole spurned a chance when, unmarked, he headed Beckham's cross wide.
Ferguson then shut up shop, replacing van Nistelrooy with Luke Chadwick and Wes Brown for Veron, the £28.1million Argentinian midfielder who in his own way had had an effective a game as the Dutchman.