The Swede struck in the 12th minute to secure all three points against the Gunners, who started the day in third place.
It was a magnificent header from Isak, who met Anthony Gordon's sensational first-time cross to ensure Eddie Howe's side followed up their midweek cup success against Chelsea with another win in the Premier League.
United triumphed by the same scoreline on Tyneside against the Gunners last term, but while Gordon's winner that day was a controversial one, even the most ardent Arsenal fan would struggle to argue that this was a deserved result for the Magpies.
Serena Taylor and Michelle Mercer brought newcastleunited.com this gallery.