Tottenham, three-times winners of the competition, suffered a humiliating 1-0 defeat by League Two Grimsby in the League Cup second round on Tuesday.
Democratic Republic of Congo striker Jean-Paul Kamudimba Kalala was Grimsby's hero in the 89th minute, lashing the ball into the net from just outside the area.
Birmingham were the night's other Premiership losers, going down 3-2 at Gillingham after extra time while Aston Villa came from 3-1 down to win 8-3 at Wycombe.
Villa, five-times League Cup winners, scored seven goals in the second half, Gareth Barry and James Milner claiming two each.
West Ham won 4-2 at Sheffield Wednesday, Charlton beat Hartlepool 3-1, Finland striker Mikael Forssell set Birmingham on the way to a 2-0 victory at Scunthorpe United and West Brom crushed Bradford City 4-1.
The eight Premier League clubs who qualified for European competition, led by holders Chelsea, join the competition in the third round next month, CNN reports.