All the pre-season talk was of Man Utd’s new look strike force, but it was a midfielder who stole the show as Everton’s Marouane Fellaini rose highest to beat David De Gea and seal all three points for the Toffees.
Tom Cleverley came closest to leveling for last season's runners up, but his shot was cleared off the line by Everton defender Phil Jagielka.
Signing Van Persie from Arsenal last week was meant to provide the additional firepower the 19-time champions need to regain the Premier League title from rivals Manchester City.
But the Netherlands striker, who cost a reported £24m, failed to even hit the target after coming off the bench in the 68th.
It was the first time Alex Ferguson's side has lost a league opener since 2004.