Burnley, Leicester and West Ham all joined Manchester United as Capital One Cup second-round casualties on a night of high drama on Tuesday night.New Manchester United boss Louis van Gaal, now without a win in three matches, watched on in misery as his team were knocked out of the League Cup 4-0 by MK Dons.
Will Grigg and Arsenal loanee Benik Afobe scored a brace apiece as United were easily downed by a team that began the night 38 places below them in the league ladder.
United were not the only Premier League side to be unceremoniously dumped out either, with three others - Burnley, Leicester and West Ham - also being beaten by lower-league opposition.
An Atdhe Nuhiu penalty gave Sheffield Wednesday a 1-0 win at Burnley, while Leicester were beaten at home, 1-0 by Shrewsbury with Andy Mangan getting the goal.
West Ham went down on penalties to League One side Sheffield United. Their fans spent the night taunting their visitors about former player Carlos Tevez - whose controversial signing kept the Hammers in the Premier League ahead of the Blades in 2007 - but it was a new expensive striker who cost them.
Enner Valencia missed the vital penalty in a 5-4 loss after Winston Reid's own goal had cancelled out Diafra Sakho's opener in normal time.
West Brom narrowly avoided a similarly embarrassing shoot-out exit as they beat Oxford 7-6 after a 1-1 draw in 90 minutes - Danny Hylton scoring for the League Two side after Johnny Mullins' earlier own goal.
Jack Cork and Graziano Pelle scored their first goals for Southampton - Cork in his 114th game and Pelle in his third - as the Saints won 2-0 at Millwall, while a John Egan own goal gave Newcastle a tight 1-0 victory at Gillingham.
Both Derby and Reading left it late to secure 1-0 successes, with Ivan Calero seeing County past Charlton and Jack Taylor giving Royals boss Nigel Adkins a winning return to Scunthorpe.
Nathan Tyson and Liam Wakefield scored either side of a Lloyd Dyer leveller as Doncaster shocked Watford 2-1 at Vicarage Road, but there was no upset for 2013 winners Swansea as they got past Rotherham 1-0 thanks to Bafetembi Gomis' first goal for the club.
Jermaine Beckford scored twice as Bolton beat Crewe 3-2 after extra-time - Darren Pratley scoring their other goal after strikes from Bradden Inman and Marcus Haber for Crewe.
Dwight Gayle gave managerless Crystal Palace a boost as he scored a first-half hat-trick as they won 3-0 at Walsall, while Brighton won 4-2 at Swindon.
Four goals shared amongst Rohan Ince and Adrian Colunga (both Brighton) and Louis Thompson and Yaser Kasim had it locked at 2-2 with 10 minutes of extra-time left, but two Jake Forster-Caskey penalties won it for the Seagulls.
At Carrow Road, Norwich saw off Crawley 3-1 with Cameron Jerome scoring his first goal for the club and Josh Murphy getting two. A Carlos Cuellar own goal accounted for Crawley's return.
It was easy for Middlesbrough in the end at the Riverside as two goals from Lee Tomlin and one from Bradley Fewster did for Preston, for whom Jordan Hugill had equalised in a 3-1 defeat.
Eleven-million pound signing Ross McCormack scored his first goal for troubled Fulham as they enjoyed a breather from the league to beat Brentford 1-0, while at Huddersfield James Vaughan climbed off the bench and put through his own goal as Nottingham Forest won 2-0, with Henri Lansbury adding the second.
Dan Gosling, Brett Pitman and Callum Wilson all scored as Bournemouth cantered to a 3-0 win over Northampton, while Federico Macheda netted twice as Cardiff triumphed 3-2 at Port Vale.
Joe Ralls got their other on a night when Michael O'Connor and Michael Brown responded for the home side.