Last year's beaten finalists Cardiff City crashed out of the Capital One Cup in the first round after blowing an early lead to go down 2-1 at npower League Two Northampton.
Heidar Helguson gave the Bluebirds a dream start by converting a second minute penalty but David Artell equalised for the Cobblers on 37 and Alex Nicholls sealed a shock win by heading home just after the restart.
Gus Poyet's Brighton were also on the end of a shock defeat as they went down 3-0 to Paolo Di Canio's newly-promoted League One Swindon at the County Ground while Bristol City were another Championship side to crash out as they were beaten 2-1 by Gillingham at Ashton Gate.
Birmingham were amongst the goals as they beat Barnet 5-1 while Leicester beat Torquay 4-0 and Peterborough beat Southend at London Road by the same score.
Crystal Palace had to come from behind to beat Exeter 2-1 at St James's Park while League Two Bristol Rovers took a surprise 26th minute lead at Ipswich through Michael Smith, before the Tractor Boys turned it round with Jason Scotland, Tommy Smith and Aaron Cresswell setting up a 3-1 win.
Burnley were yet another Championship side forced to come from behind as Chris McCann, Charlie Austin and Dean Marney cancelled out an early Chris Shuker effort in a 3-1 win at Port Vale.
Crisis club Portsmouth crashed 3-0 at Plymouth, while another newly-relegated side, Coventry, squeaked past League Two Dagenham & Redbridge with Kevin Kilbane's injury-time penalty.
League One Stevenage beat AFC Wimbledon 3-1 and Yeovil won an all-League One clash 3-0 at home to Colchester.
League One Scunthorpe staged a stupendous comeback to knock out Championship Derby 7-6 on penalties at Pride Park after a 5-5 draw in normal time while newly-promoted Charlton were another Championship side to fall as they went down 4-3 on penalties to League One Leyton Orient at The Valley.
Millwall also missed out on penalties to League One Crawley Town at the New Den, Abdulai Bell-Baggie scored in the last minute of extra-time to give Tranmere a 2-1 win at Chesterfield, while League Two Oxford pulled off a minor upset with a 5-3 penalty win over Bournemouth after a goalless draw.