And that crucial first-half header proved enough to end the Hammers' hoodoo over the Gunners.
Unbeaten against Arsenal for the past two seasons, the East Enders had been the last-ever team to win at Highbury and the first visitors to record a victory at the Emirates Stadium, too, while also managing to sandwich another ill-tempered three points at Upton Park between those two away successes.
Both clubs had secured Carling Cup fourth round berths in midweek, but having made eight changes for Tuesday's 2-0 victory over Newcastle United, Arsene Wenger ensured that only Philippe Senderos survived the mass cull that saw him discard no less than ten of the young guns.
And returning to the more serious business of consolidating the Gunners' position at the top of the Premier League tree, the Frenchman was delighted to see van Persie out-jump Lucas Neill and put his side into that 13th minute lead with a downward header.
His effort sneaked inside the foot of the diving Robert Green's right-hand post after Emmanuel Adebayor invited Alex Hleb to float a right-wing cross into the danger zone.
The Dutchman's strike was a devastating early blow for the seventh-placed Hammers, who had made six changes following the last-gasp victory over Plymouth Argyle three days earlier.
Having handed a full debut to Henri Camara and welcomed back Green, Matthew Upson, Anton Ferdinand, Mark Noble and Lee Bowyer, manager Alan Curbishley went on to endure an uncomfortable first half that saw Hammers barely threaten.
Meanwhile, Bowyer and Noble were booked for nasty lunges on Mathieu Flamini and the consequently stretchered away Hleb.
Indeed, apart from Dean Ashton's rising 20-yarder that just cleared the crossbar of the otherwise untroubled Manuel Almunia, it was the domineering Gunners who continued to threaten, as Green saved two rasping efforts from Flamini, before beating van Persie's adept, angled, byline free-kick aside.
Having lost Scott Parker with a tweaked knee at the interval, Curbishley then saw Ferdinand limp away with a hamstring pull just after the restart and.
However, but for the fingertips of the flying Green, the afternoon would have got even worse as the keeper athletically tipped van Persie's 20-yard curler onto his left-hand post.
As the hour-mark approached, Almunia was finally called into his first save of the afternoon when Ashton sent a point-plank header into his midriff.
Former Gunner Freddie Ljungberg then had an effort ruled out by a controversial offside flag that Curbishley publicly questioned afterwards.
Green had single-handedly kept the Hammers in the match during last April's sensational victory at the Emirates Stadium and, yet again, he went on to shoot down the attack with an impressive array of agile stops to thwart Adebayor, Gael Clichy and Flamini.
Chasing just that single-goal deficit, though, West Ham still threatened through Ashton, who went close with a 25-yarder that sizzled just inches wide and then the in-form striker saw his downward header ironically hooked clear by match-winner van Persie.