Sheffield Wednesday produced one of the shocks of this season's Capital One Cup to reach the quarter-finals as they stunned Arsenal with a 3-0 victory at Hillsborough.
On a damaging night for Arsenal, the Premier League side lost both Alex Oxlade-Chamberlain and his replacement Theo Walcott to injury within the first 19 minutes of the match.
The Gunners' woe was further compounded as the Championship side raced into a 2-0 lead at the break thanks to goals from Ross Wallace and Lucas Joao.
Carlos Carvalhal's side continued where they left off after the interval as Sam Hutchinson bundled home Kieran Lee's cross to inflict Arsenal's worst defeat to lower-league opposition in 56 years and send Sheffield Wednesday cruising into the last eight for the first time since 2002.
Wenger, who handed debuts to Alex Iwobi and Glen Kamara, made eight changes to the side that beat Everton 2-1 at the weekend with Petr Cech, Olivier Giroud and Oxlade-Chamberlain the only survivors.
In front of 36,065 fans at Hillsborough, Arsenal looked to stamp their authority on the game in the early stages but they were hampered when Oxlade-Chamberlain left the field in the fifth minute with a tight hamstring.
He was replaced by England colleague Walcott but he too soon pulled up - clutching his calf - and was eventually replaced by Ismael Bennacer.
The night got worse for the Premier League side when Sheffield Wednesday - backed by strong support from the Hillsborough crowd - took the lead in the 28th minute through Wallace. Barry Bannan released Pudil down the left and from his cut-back, Wallace curled the ball beyond Cech and into the bottom corner.
Hillsborough was rocking and Wallace was only inches away from a second minutes later, curling a 20-yard free-kick just wide.
Wednesday were now full of confidence and Arsenal needed Cech to keep out Jeremy Helan's effort. However, he could not repel Joao's powerful 40th-minute header, Wallace turning provider from Helan's short corner.
The Gunners were back out after the interval well before their hosts, clearly keen to stage a second-half comeback, but any such hopes were dashed six minutes after the restart as Hutchinson made it three.
Bannan clipped a free-kick to the far post where Tom Lees was unmarked and his ball back across goal was easily scooped home by Hutchinson.
Arsenal enjoyed plenty of the ball, but they rarely tested rookie Wednesday goalkeeper Joe Wildsmith, who was a spectator for much of the final 30 minutes.
The one time Wildsmith was called into action, he superbly turned Per Mertesacker's header over the bar as Wednesday saw out a famous win - a ninth game in all competitions without defeat and a second successive Premier League scalp following a third-round victory at Newcastle.
It means that Arsene Wenger's wait for a first League Cup of his lengthy reign goes on and the Gunners have not won this competition since 1993, when they were victors over the Owls at Wembley.