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For the second time in a Premiership game at Old Trafford this season, the Reds needed a Van Nistelrooy penalty to bag three points.
As in their games against West Brom, Middlesbrough and Bolton before, United struggled to break down their opponents with Spurs goalkeeper Kasey Keller and central defender Dean Richards outstanding in the Tottenham rearguard.
The only goal of the game came in the 63rd minute when Ole Gunnar Solskjaer was unceremoniously upended by Gary Doherty in the Tottenham box.
Referee Rob Styles pointed to the spot and Van Nistelrooy sent Keller the wrong way when he slotted his penalty low and right footed into the bottom left corner of the net.
United had had good claims for a penalty denied seconds earlier when Doherty appeared to bring down Van Nistelrooy in the box, but Mr Styles waved away United's appeals.
It was a mixed game for Van Nistelrooy, who was booked along with Richards for some tussling in the Tottenham penalty area after 27 minutes.
Keller made several fine saves. In the 23rd minute he blocked a powerful David Beckham effort with his legs and surpassed that stop 13 minutes later with a flying effort to tip away a blistering Solskjaer shot.
After the interval, the American again denied the Reds, twice saving superbly from Solskjaer and also foiling Van Nistelrooy.
At the other end, United's goalkeeper Fabien Barthez was in equally fine form. The Frenchman raced 30 yards from his goal to tackle Robbie Keane in the 53rd minute after a slip by Rio Ferdinand had let him in.
Five minutes later, Barthez saved a point-blank effort from Richards with his legs on the six-yard box.
But then in the old days at Old Trafford, home goalkeepers were seldom man of the match.