Wenger had endured countless frustration in his previous battles with his Portuguese nemesis, but goals from Granit Xhaka and former United striker Danny Welbeck ended his hoodoo against Mourinho.
In 12 previous Premier League games against Mourinho the Arsenal boss had been unable to mastermind a victory, suffering five defeats and picking up seven draws.
The closest Wenger had previously come to beating Mourinho was in December 2006 when Michael Essien scored an 84th minute equaliser for Chelsea in a 1-1 draw at Stamford Bridge.
Mourinho also inflicted a 6-0 mauling on Wenger during his second spell as Chelsea manager in March 2014 before he took over as United boss in the summer of 2016.
Olivier Giroud’s 89th minute goal spared Wenger defeat against his old foe at Old Trafford earlier this season before he finally had cause to celebrate a win in a key game in the race for Champions League qualification.
13 - Arsene Wenger has beaten Jose Mourinho in the Premier League at the 13th attempt (D7 L5). Hex. pic.twitter.com/C4t3PiKnOJ— OptaJoe (@OptaJoe) 7 de mayo de 2017
Xhaka’s deflected strike on 54 minutes broke the deadlock and, just three minutes later, the unmarked Welbeck headed home to breathe life into Arsenal’s quest to finish in the top four.
In addition to getting one over Mourinho for the first time, Wenger’s side’s victory also ended United’s 25-match unbeaten run in the Premier League.