Watford were the victims of a League Cup giant-killing as the Premier League side lost 1-0 at Championship club Preston in the second round on Tuesday.
Hornets manager Quique Flores made 11 changes to the team whose goalless stalemate against Southampton on Sunday made it three successive draws since their return to the Premier League.
Flores's gamble backfired as Watford became the only one of the 11 Premier League teams in action on Tuesday who failed to make the third round.
On-loan Sheffield Wednesday defender Marnick Vermijl slotted in the close-range winner in the eighth minute and Watford's woes were compounded when debutant Miguel Britos was sent off in the 75th minute for violent conduct after the Uruguayan defender lashed out with his elbow.
Stoke were pushed to the brink of a shock exit before beating fourth tier Luton 8-7 on penalties after a 1-1 draw at Kenilworth Road.
Mark Hughes' side, who had former Barcelona forward Bojan back for the first time since January after a knee injury, went ahead through Jon Walters 67th minute goal, only for Cameron McGeehan to force extra-time with a 90th minute equaliser.
In the shoot-out Luton's Scott Griffiths hit the bar at 7-7 and Stoke's Geoff Cameron drilled in the winner.
West Bromwich Albion also required penalties to defeat third tier Port Vale at the Hawthorns.
Albion were without Tottenham target Saido Berahino, the England Under-21 striker who has handed in a transfer request, and they couldn't break down the Vale defence in a 0-0 draw after extra time before taking the shoot-out 5-3.
Jermain Defoe's hat-trick spared Sunderland's blushes as the Premier League strugglers defeated fourth tier Exeter 6-3 at the Stadium of Light.
Dick Advocaat's side have failed to win any of their first three league games and they blew 2-0 and 3-2 leads before finally avoiding further embarrassment.
- Treble -
Aston Villa were also indebted to a hat-trick hero as Scott Sinclair inspired a 5-3 win over fourth tier Notts County after extra-time.
Genaro Snijders' 16th minute deflected strike put County ahead.
Teenage forward Adama Traore marked his first Villa start with the equaliser as the recent £7 million signing from Barcelona slotted home in the 24th minute.
Jon Stead's penalty in first half stoppage-time put County back in front.
Sinclair equalised in the 50th minute, only for Graham Burke to put County ahead again with a superb long-range effort six minutes later.
But Villa's extra quality paid off as they levelled through Sinclair's 78th minute penalty before the former Manchester City winger completed his treble in the 99th minute.
Joe Bennett's 111th goal put a flattering look on the scoreline for last season's FA Cup runners-up.
French winger Florian Thauvin marked his first Newcastle start with a goal in a 4-1 win against fourth tier Northampton.
Thauvin, a £12 million ($18.8 million, 16.6 million euros) signing from Marseille, bagged a third minute goal at St James' Park and Siem De Jong's header put the hosts further in front five minutes later.
Marc Richards' penalty reduced the deficit before Daryl Janmaat and Mike Williamson struck in the second half for Steve McClaren's men.
Crystal Palace needed extra-time to see off League One side Shrewsbury, who had taken the lead through Matt Tootle before penalties from Dwight Gayle and Glenn Murray and Lee Chung-yong and Wilfried Zaha strikes sealed a 4-1 win for the hosts.
Ghanaian forward Joe Dodoo, 20, hit a debut hat-trick as Leicester maintained their flying start to the season with a 4-1 win at third tier Bury.
Norwich flop Ricky Van Wolfswinkel scored only his second goal for the Canaries in their 2-1 win at Rotherham.
Swansea, who won the competition in 2013, defeated York 3-0, while Bournemouth also beat fourth tier opposition, winning 4-0 at Hartlepool.
Source: AFP
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