Marc McNulty’s second-half strike sent League One Sheffield United into the League Cup semi-finals at the expense of Southampton.
The Saints struggled throughout and United’s Jamal Campbell-Ryce and Louis Reed both went close in the first half.
Sadio Mane shot wide for the visitors, but McNulty poked in after Fraser Forster failed to hold a free-kick.
Florin Gardos was sent off late on to compound Southampton’s misery as the hosts secured a famous win.
It continued Sheffield United’s impressive record against Premier League opposition in cup competitions, having knocked out Aston Villa, Fulham, West Ham and now Southampton in the last two seasons.
“It is an incredible night for the club,” said Sheffield United manager Nigel Clough.
“I thought we deserved the victory, we created more chances and the only disappointment was that we should have had another goal.
“Whoever we get in the semi-final will be a special occasion, but nights like tonight stay in the memory for a long time.”
For Southampton it extended their poor run of form in recent weeks.
They had lost their four Premier League fixtures prior to the trip to Bramall Lane and Sheffield United, FA Cup semi-finalists last season, sensed the chance of an upset from the outset.
With just two defeats in their 17 previous cup games under Clough they immediately set about extending that fine record as Campbell-Ryce saw a free-kick end up on top of the bar, while Reed sent a well-struck effort just over.
And in the second game played, Filipe Luis struck his first Chelsea goal with a brilliant free-kick to help secure a League Cup semi-final place with a win at 10-man Derby, reports the BBC.
Eden Hazard put the Premier League leaders in front and Luis made it 2-0.
Craig Bryson gave Derby hope, but Jake Buxton was harshly sent off before Andre Schurrle wrapped up victory.
Chelsea centre-back Kurt Zouma suffered a head injury and striker Didier Drogba hobbled off, but neither was a serious problem, boss Jose Mourinho said.
Derby centre-back Buxton had a night to forget, having given the ball away before Hazard exchanged passes with Cesc Fabregas and drilled a perfectly-placed shot into the corner of the net for Chelsea’s 23rd-minute opener.