The 29-year-old Dutchman, relegated to the substitute's bench for the Carling Cup Final and United's last five Premiership matches, struck with his 23rd goal of the season in the dying seconds of the first half.
Ji-Sung Park raced past West Ham full-back Paul Konchesky as he cut in from the wing into the right side of the penalty area.
The South Korean pulled his low cross back to the near post where van Nistelrooy directed his low right-foot shot from the edge of the six-yard box into the far corner of the net.
The result reduced Chelsea's lead at the top to nine points over United, but more importantly for Sir Alex Ferguson's side are now five points clear of third-placed Liverpool with a game in hand.
However, United were made to fight for their victory by a determined West Ham side although, despite the narrow winning margin, it was always United who looked the more menacing in front of goal.
West Ham's best spell of the game came in the opening seven minutes when Matthew Etherington, Hayden Mullins and Dean Ashton all went close.
But United soon came to life and Cristiano Ronaldo's blistering 30-yard free-kick was taken at the second attempt by Hammers goalkeeper Shaka Hislop.
In the 23rd minute, Wayne Rooney's crisp pass from the left found Darren Fletcher racing into the Hammers box, but his shot from 12 yards ended up in the side-netting.
A glorious one-two between Ronaldo and Rooney opened the way for van Nistelrooy to get in a shot which was blocked.
United youngster Gerard Pique produced a surprise 25-yard power-drive which almost caught Hislop napping and United went even closer after 34 minutes.
Park's corner was flicked on by Rio Ferdinand at the near post and his fellow central defender Nemanja Vidic fired in a shot from 12 yards which rebounded off the foot of a post.
Ronaldo flicked from the left wing in the 38th minute and his exchange of passes with Patrice Evra ended with the Frenchman driving in a shot which Hislop again fumbled, before recovering just in time to block the full-back's follow-up effort.
After van Nistelrooy's goal, United tightened their control of the game after the interval.
Superb inter-passing between Evra, Park and Rooney created another opening for van Nistelrooy, whose 48th minute shot from the edge of the penalty area hit Hislop on the chest.
Hislop did well to keep out a deflected 20-yard drive from Ronaldo, while Vidic headed a Park corner straight at the Trinidad goalkeeper.
United should have increased their lead in the 74th minute. Pique found Ronaldo on the right and another surging run ended with him pulling the ball back from the by-line to Rooney, whose first-time shot from 12 yards hit the bar.
The rebound fell to van Nistelrooy, whose quick-thinking overhead kick at the far post went straight at Hislop.