Rotherham upset local rivals Sheffield Wednesday with a 2-1 win.
Ben Pringle put the Millers ahead before Rhys McCable levelled for the visitors.
Lee Frecklington put the hosts back in front before Wednesday substitute Jermaine Johnson was sent off for a headbutt on Pringle.
Last season's beaten finalists Bradford made an early exit from the Capital One Cup as they suffered a 2-1 defeat at Huddersfield.
The Bantams enjoyed a dream run to February's Wembley final thanks to victories over Wigan, Arsenal and Aston Villa, but there will be no repeat after a double from James Vaughan gave the Terriers victory, despite Nahki Wells' late strike.
Championship Middlesbrough suffered a shock defeat as they were beaten 2-1 by League Two Accrington at the Riverside Stadium.
Lukas Jutkiewicz had put the hosts ahead but Marcus Carver and Piero Mingoia hit back to give Stanley a famous win.
Ipswich were another second-tier side to be dumped out by lower-league opposition as they fell to a 2-0 defeat at Stevenage.
A penalty from Filipe Morais early in the second half put Stevenage ahead, with Jordan Burrow sealing the win.
Watford were comfortable 3-1 winners at Bristol Rovers. A brace from Sean Murray and a Gabriele Angella strike put the Hornets in control before Eliot Richards pulled one back for Rovers.
Michael Jacobs got the only goal as Championship Derby won at Oldham, while David Jones, Junior Stanislas, Danny Ings and Scott Arfield all found the net as Burnley won 4-0 at York.
Sean St Ledger netted a stoppage-time winner as Leicester edged to a 2-1 win at Wycombe.
Jo Kuffour equalised for Wanderers after David Nugent's penalty, only for St Ledger to sink their hopes of an upset.
Kevin Dawson's goal gave Yeovil a 1-0 win at Southend and Ryan Williams did likewise for Morecambe in their home win over Wolves by the same scoreline.
Eunan O'Kane ensured Championship Bournemouth prevailed 1-0 over League Two Portsmouth in their south coast derby.
Simon Church struck twice for Charlton as the Addicks claimed a comfortable 4-0 success against Oxford with Danny Green and Jordan Cook also on the scoresheet.
Charlie Austin netted on his full debut and Danny Simpson also grabbed a goal as QPR won 2-0 at Exeter, while Nottingham Forest eased to a 3-1 win over Hartlepool as Radoslaw Majewski, Greg Halford and Matt Derbyshire all scored.
Sam Baldock and Jordan Wynter helped Bristol City to a 2-0 win at Gillingham, while Andy Keogh and Martyn Woolford were on target for Millwall in their 2-1 win over AFC Wimbledon.
There was more woe for Coventry after their recent off-field troubles as Kevin Lisbie's late winner gave Leyton Orient a 3-2 win over the 10-man Sky Blues.
Coventry had trailed 2-1 and were a man down after goalscorer Carl Baker was sent off.
Franck Moussa pulled them level, but they were undone by Lisbie's last-gasp effort, the striker's second of the game.
Kyle Bartley came to Birmingham's rescue against Plymouth at St Andrew's.
The on-loan Swansea defender struck the winner in the second minute of extra-time to give the Blues a 3-2 win. Scott Allen had earlier got a brace for the hosts, with Lewis Alessandra producing a double of his own for Argyle.
Farid El Alagui scored a late winner as Brentford beat Dagenham 3-2, while Bury beat Crewe by the same scoreline.
Bongani Khumalo got the only goal to see Doncaster past Rochdale, while Peterborough were emphatic 5-1 winners at Colchester and Byron Harrison's extra-time strike saw Cheltenham win 4-3 in a thriller against Crawley.
Newport, fresh from winning on their return to the Football League, enjoyed a stunning 3-1 win at Championship Brighton after extra time.
County had trailed to an Ashley Barnes strike only for Albion to have Inigo Calderon dismissed halfway through the second half.
Danny Crow levelled for the Welsh club before adding a second in extra time, with Conor Washington sealing the win for Justin Edinburgh's side.
Elsewhere, Bolton won 3-1 at Shrewsbury and MK Dons beat Northampton 2-1, with Burton beating Sheffield United and Walsall edging Port Vale by the same score.
Andy Williams' goal saw Swindon beat Torquay 1-0, and Tranmere defeated Mansfield 2-0.
Barnsley needed penalties to see off League Two Scunthorpe in their tie. Chris O'Grady kept his nerve to seal a 5-4 shootout win for the Tykes after 120 goalless minutes. Niall Canavan was the man with the critical miss for the Iron.