Premier League high-flyers Newcastle suffered a shock FA Cup exit against Sheffield Wednesday and holders Liverpool rode their luck in a draw with Wolves, while Nottingham Forest and Bournemouth crashed out on a day of third round surprises.
Elsewhere on an enthralling afternoon of FA Cup action, Ryan Reynolds and Rob McElhenney, the Hollywood actors who co-own Wrexham, led the celebrations on social media after their non-league side's surprise 4-3 victory at second tier Coventry.
But it was Wednesday, second in League One, who stole the show on Saturday with their impressive 2-1 victory at Hillsborough against a Newcastle team sitting third in the Premier League.
Eddie Howe's side were unbeaten in 15 games, but Wednesday have now gone undefeated in 10 matches after Josh Windass's double stunned the Magpies.
Wednesday went ahead in the 52nd minute when Windass, who looked in an offside position, diverted Dennis Adeniran's ball across from close-range.
Windass scored his second 13 minutes later, coolly converting after being put through by Michael Smith.
Newcastle reduced the deficit in the 68th minute when Bruno Guimaraes poked home from close-range, but Chris Wood squandered a golden opportunity to equalise as he fired over from 10 yards.
"It was a disappointing result for us. We are aware that we don't have the deepest squad of any team in the Premier League," Howe said.
At Anfield, a difficult week for Liverpool that started with a Premier League loss at Brentford, concluded with a fortuitous 2-2 draw against Wolves.
Liverpool keeper Alisson Becker was guilty of a woeful error when his pass was intercepted by Goncalo Guedes, who slotted Wolves' 26th minute opener.
Darwin Nunez cushioned a superb volley past Matija Sarkic to equalise on the stroke of half-time and Mohamed Salah's deft finish in the 52nd minute put Liverpool ahead.
But the Reds, who gave a debut to Netherlands forward Cody Gakpo after his move from PSV Eindhoven, were pegged back in the 57th minute through Hwang Hee-chan's composed effort.
It could have been even worse for Liverpool, as Toti's goal was disallowed for offside in the final minutes as the Reds survived for a replay.
"The first goal should not happen, but we all know how often Ali saves our backsides," Liverpool boss Jurgen Klopp said.
"I'm not sure about their disallowed goal. We have one picture where it may look offside, but I can understand why they are angry about it."
Wolves manager Julen Lopetegui was furious with the decision and also claimed Salah's strike should have been ruled out.
"We have seen it, the offside doesn't exist, I'm sorry. It's impossible. The decision is wrong," he said.
"Then Mohamed Salah was offside before Toti touched the ball, so he got an advantage."
- 'Great chapter' -
Sam Dalby, Elliot Lee, Thomas O'Connor and Paul Mullin scored for National League side Wrexham as they swept into a 4-1 lead at Coventry.
Despite a late fightback from 10-man Coventry, Wrexham reached the fourth round for the first time since 2000, sparking a celebratory Instagram post from Reynolds laced with profanity.
"It's a great chapter in the story of Wrexham since the new owners have come in and I'm sure they will be overjoyed with what they've seen today," Wrexham boss Phil Parkinson said.
Forest boss Steve Cooper named an entirely different starting team for the match at Blackpool after his side's midweek win against Southampton, which lifted them out of the Premier League relegation zone.
The plan backfired badly as the Championship team won 4-1 at Bloomfield Road, with goals from Marvin Ekpiteta, Ian Poveda, CJ Hamilton and Jerry Yates.
Two goals each from Anass Zaroury and Manuel Benson put Championship leaders Burnley on course for a 4-2 win at Bournemouth.
Harry Kane moved closer to becoming Tottenham's all-time record goalscorer as he netted in the 50th minute of a 1-0 win against Portsmouth.
Kane, with four goals in four matches since missing the penalty against France that led to England's elimination at the World Cup, has 265 goals for Spurs -- just one behind the club's all-time record scorer, Jimmy Greaves.