Charlie Austin shattered Arsenal's 22-game unbeaten run as the Southampton striker punished a howler from Gunners goalkeeper Bernd Leno to seal a shock 3-2 win on Sunday.
Austin settled a thrilling Premier League clash at St Mary's when he headed home with just five minutes left after Leno misjudged Shane Long's cross.
Southampton had twice taken the lead through Danny Ings, only for Henrikh Mkhitaryan's brace to draw Arsenal level on each occasion.
Leno's mistake and Austin's predatory finish handed Arsenal their first defeat in 15 league games and brought a stunning halt to their longest unbeaten run in all competitions since 2007.
Unai Emery's fifth placed team hadn't lost since a 3-2 defeat at Chelsea in August and the north Londoners' first setback since the summer leaves them two points behind the fourth placed Blues, who won at Brighton on Sunday.
Laurent Koscielny was making his first Premier League start since April after recovering from an Achilles injury, but Arsenal's French centre-back looked rusty when Southampton took a surprise lead in the 20th minute.
Matt Targett whipped over a superb cross and Koscielny was caught by Ings' perfectly-timed run, completely missing his attempted clearance as the on-loan Liverpool striker powered his header past Leno.
It took Arsenal just eight minutes to equalise with a flowing move that saw Alex Iwobi pick out Nacho Monreal's run before the Spaniard chipped a cross for the unmarked Mkhitaryan to head home.
Ings' movement was causing Arsenal problems and he struck again to restore Southampton's lead in the 44th minute.
Nathan Redmond's cross unhinged Emery's creaky back-three and this time Ings got in between Koscielny and Stephan Lichtsteiner to loop a fine header over the stranded Leno.
The Gunners have been far more dangerous after the interval this season and once again they hit back to equalise in the 53rd minute.
Allowed too much space on the edge of the area, Mkhitaryan collected Lacazette's pass and drilled a low strike that took a crucial deflection off Jannik Vestergaard as it flashed past the wrong-footed McCarthy.
Hasenhuttl was celebrating again as Southampton punished Leno's blunder to snatch the points in the 85th minute.
Long's cross floated across the penalty area, tempting Leno off his line, but the German missed with his attempt to punch clear and Austin was on hand to head into the empty net.
Meanwhile, Chelsea consolidated fourth place in the Premier League with a 2-1 win at Brighton & Hove Albion that became harder work than had seemed likely in the first half.
Eden Hazard set up the first goal for Pedro after 17 minutes and scored the second himself before halftime following a defensive error.
Brighton came back into contention through Solly March's goal midway through the second half and Lewis Dunk went close to an equaliser.
Chelsea moved three points clear of London rivals Arsenal, who were beaten at Southampton.