The Netherlands striker had gone 10 United matches without scoring before slamming home a 66th-minute penalty — his 20th goal of the campaign — to add to midfielder Michael Carrick 's opening goal from close range in the fourth minute.
By successfully recovering from the derby defeat to Manchester City on Monday, United needs only seven more points from its last six matches to clinch a 20th English championship. That would also require second-place City winning all seven of its remaining games.
Van Persie is likely to win a maiden title in his first season at Old Trafford, and he has arguably done more than anyone to help rip the trophy from City's grasp. However, his goals — if not his impressive performances — had dried up of late and he was in the midst of his driest spell in nine years in English football.
The relief on his face was understandable then, as he sprinted down the touchline after slotting the spot kick past Asmir Begovi c and headed straight for Alex Ferguso n. The manager has kept faith in the Dutchman, who lifted him up after a hug and then high-fived teammates.
It was just as happy a day for Wayne Rooney , who was given a rare start in central midfield by Ferguson and gave a masterful display, controlling play with class, poise and a wonderful range of passing.
In fairness, Rooney was given an easy ride by the hosts, whose famed physical approach was distinctly lacking on a bitterly cold and windy afternoon in the midlands. Their midfield was toyed with and they offered precious little in attack, leaving under-fire manager Tony Pulis with plenty to ponder in the forthcoming relegation battle.
Having regressed in the league in each of its past three seasons, Stoke has dropped to fifth from bottom and remains just three points from the relegation zone. With only one win in its last 14 matches, Stoke has the worst record in the league in 2013.
While Rooney was the standout player, at least in a one-sided first half, it was his central-midfield partner who put United ahead with a rare goal.
It was a scrappy one, with Van Persie's inswinging corner causing all sorts of mayhem. Stoke failed to clear and the ball bobbled toward Carrick, who stabbed a low finish beyond Begovic's despairing dive for United's 100th goal of the season in all competitions.
Rooney curled a free kick just past the post, Van Persie's audacious effort from 50 yards drifted wide while Stoke's attacks continued to peter out. United center backs Rio Ferdinand and Nemanja Vidic will never have had a more comfortable half at Britannia Stadium.
Playing against the wind in the second half didn't halt United's momentum, and Van Persie will be disappointed he didn't test Begovic when he was played through out wide by Javier Hernandez.
Jonathan Walters hooked a shot over and Charlie Adam brought an easy save out of United goalkeeper David de Gea as Stoke finally began to show signs of attacking intent near the hour mark.
But Van Persie soon ended any hopes of a comeback, picking himself up after being tripped by Ryan Shawcross in the 65th and drilling a low penalty into the right corner. It was his first goal since United's second in a 2-0 win over Everton on Feb. 10 — and he let Ferguson know about it.