Humiliated by fourth-tier Bradford in the League Cup quarterfinals in December, Arsenal left to jeers from its own despairing supporters after Colin Kazim-Richards stabbed home a 72nd-minute winner at Emirates Stadium to create the latest big surprise in the FA Cup.
Wenger had never previously lost to a lower-division team in the famous old competition in his 17 years at the London club.
"It's painful and disappointing to lose a game like that," said Wenger, whose gamble in resting many of his top players ahead of Tuesday's Champions League last-16 first leg against Bayern Munich completely backfired. "It's very difficult to accept."
The Champions League is the only trophy Wenger's men have left to play for — and they are big underdogs in that competition, too, especially after this lacklustre display. The club's last trophy was the FA Cup in 2005.
The shocks didn't end there, with third-tier Oldham grabbing an equalizer deep into stoppage time to draw 2-2 with Everton. That earned the team a lucrative replay at Goodison Park and continued an impressive run that has already seen it eliminate Liverpool.
Luton failed in its bid to become the first non-league team to reach the FA Cup quarterfinals in 99 years by losing 3-0 at home to Millwall, and Barnsley beat MK Dons 3-1 in another match between lower-league clubs.
After four of eight matches in the fifth round, there are still no topflight teams assured of a place in the quarterfinals.
Liverpool, Tottenham and Newcastle are among the Premier League teams to have been upset by lower-tier opponents this season, which is proving to be one for the underdogs with top teams seemingly focusing on the league and their European campaigns. Bradford plays Swansea in a surprise lineup for the League Cup final at Wembley Stadium next weekend.
Wenger cut a forlorn figure as he faced the press more than an hour after the final whistle, saying the Bayern match offered his team a chance at redemption.
"The season is not over," Wenger said. "For you, (but) not me."
Ironically, Kazim-Richards — a boyhood Arsenal fan and former youth-team player — stabbed home the scrappy winning goal off the post less than 60 seconds after Jack Wilshere, Santi Cazorla and Theo Walcott had been thrown on from the bench in a desperate attempt to avoid a replay.
Gervinho, playing for the first time since returning from African Nations Cup duty with the Ivory Coast, slipped a one-on-one chance wide in the first half and Tomas Rosicky smashed a fierce shot against the bar after the break in Arsenal's best chances.
But the hosts were undone on a counterattack when Blackburn winger Martin Olsson brought a save out of goalkeeper Wojciech Szczesny, only for the ball to rebound out to Kazim-Richards, who prodded down and up into the corner.
A late flurry of attacks petered out lamely for Wenger's side, which produced one of its weakest performances of a gloomy season in which the team lies fifth in the Premier League — 21 points off leader Manchester United.
"We had 11 internationals on the pitch at the start and when we made the changes, it was 0-0," said Wenger, defending a team selection that left many supporters accusing the Frenchman of disrespecting the FA Cup.
Blackburn manager Michael Appleton — coaching a third different team in this season's competition after spells at Portsmouth and Blackpool — said it was just "one of those years" in the FA Cup.
"We had a feeling they may rest their (top) players," he said. "They have a big game in the Champions League next week.
"We got an extra spring in our step when we were defending the lead."
Everton looked like it would survive a serious examination at Boundary Park when goals by Victor Anichebe and Phil Jagielka helped overturn an early lead given to Oldham by Jordan Obita.
However, in the game's last act four minutes into injury time, Matt Smith leapt highest in a crowded penalty area containing Oldham goalkeeper Dean Bouzanis to keep the hosts in the competition.
At Kenilworth Road, Luton's surprise run in the competition came to an end after first-half goals by James Henry and Rob Hulse were added to by Dany N'Guessan's close-range strike in the 86th. In the fourth round, Luton beat Norwich 1-0 to become the first non-league side to eliminate topflight opposition in the FA Cup in 24 years.
"They have had some giant-killing experience and it was a very professional job done by us," said Millwall manager Kenny Jackett, who has led his team to a first quarterfinal appearance since 2004 — the year it reached the final.
Chris Dagnall scored twice for Barnsley, the 2008 semifinalist, in its win at 10-man MK Dons to become the third second-tier team through.
Manchester City and Manchester United have home matches against Leeds and Reading, respectively, on Sunday, when Chelsea hosts Brentford in a fourth-round replay.