With second-place Manchester City beating Wigan 1-0, United’s advantage over its neighbor was reduced to 13 points with five games to go for the leaders.
Antonio Valencia scored his first goal in a year to first pull United level by canceling out Ricardo Vaz Te’s opener.
After Mohamed Diame had put West Ham in front at the start of the second half with a curled drive into the far corner, Van Persie responded with his first goal from open play in two months. It was United’s second setback in three league matches, with the 2-0 victory Sunday over Stoke preceded by a 2-1 loss to City.
With there being no doubt about the ultimate destination of the trophy, such certainty seemed to breed complacency within Alex Ferguson’s team early on at Upton Park.
West Ham had already threatened David de Gea’s goal twice – with Andy Carroll shooting narrowly wide and James Collins going close with a header – before finding the net in the 16th minute.
A team often derided for its long-ball game produced a slick counterattack, with Diame seizing possession inside his own half, charging forward and beating Carrick by the halfway line and then continuing to advance.
Matt Jarvis was picked out on the left flank and took on the United defense, before reaching the byline and chipping the ball back to the center. Carroll connected with a downward header for Vaz Te to find the final touch, nodding into the net from close range.
But United sliced West Ham apart with as much ease for the equalizer 15 minutes later.
Shinji Kagawa worked his way down the left flank and knocked the ball back to Valencia, who had the simple task of tapping in his first goal for a year.
West Ham went close through a volley by Andy Carroll that landed on the roof of the net, but it regained the lead in the 55th when Diame spun to collect a pass from Guy Demel and curled the ball in from the edge of the area.
It jolted United into action, and goalkeeper Jussi Jaaskelainen came under increasing pressure from United’s strike force.
First, van Persie was denied, then Rooney’s strike was saved by the goalkeeper but, as the ball trickled backward, Gary O’Neill sprang into action to make a goal-line clearance.
Van Persie’s header was then tipped over by Jaaskelainen, but he eventually hit the target in the 77th. Kagawa’s strike came off both posts before Van Persie pounced on the rebound and withstood Winston Reid’s block to score.
United couldn’t produce a winner, but just six points are required from the last five games before the trophy can return to Old Trafford.