Mikel Arteta's men had already fallen to the Irons' superiority twice this season, losing 3-1 in the fourth round of the EFL Cup before a shock 2-0 Emirates defeat in the Premier League in December.
However, David Moyes's men went into Sunday's London derby having not won another game since that success over the Gunners, and they were torn to shreds in a historic afternoon in the capital.
Arsenal were not able to unlock the door straight away, but the visitors' deserved opener arrived when William Saliba headed home from a Declan Rice corner, which sparked an unrelenting barrage of attacks from the electrifying visitors.
Bukayo Saka's penalty, Gabriel Magalhaes's header and Leandro Trossard's curler propelled Arsenal into a stunning 4-0 advantage by half time, seeing the Gunners lead a Premier League away game by at least four goals at the break for the first time since their 4-4 draw with Newcastle United in 2011.
There would be no such capitulation from the North London giants this time around, though, as Saka fired home the visitors' fifth before ex-West Ham captain Rice returned to haunt his former employers with a sixth from long range.
By virtue of putting six past Moyes's meek men without reply, Arsenal have registered their biggest away win in Premier League history, as well as their joint-largest away success in league history.
Prior to Sunday's slaying, Arsenal's previous best away wins in the Premier League were 6-1 batterings of Middlesbrough and Everton, the latter of which occurred in 2009 with Moyes in charge of the Toffees.
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