Arsenal defeated last year's finalists 2-1, with Mathieu Flamini striking either side of Calum Chambers's 56th minute own goal at White Hart Lane.
Cup holders Chelsea thumped Walsall 4-1 courtesy of efforts from Ramires, Loic Remy, Kenedy and Pedro. James O'Connor was on target for the League One outfit at The Banks's Stadium.
Manchester United outclassed Ipswich 3-0, with Wayne Rooney, Andreas Pereira and Anthony Martial finding the net at Old Trafford.
Liverpool ousted fourth-tier Carlisle 3-2 on penalties after Derek Asamoah cancelled out Danny Ings' opener for the Reds in regulation time at Anfield.
Results: Tottenham 1-2 Arsenal
Walsall 1-4 Chelsea
Crystal Palace 4-1 Charlton
Norwich 3-0 West Brom
MK Dons 0-6 Southampton
Newcastle 0-1 Sheff Wednesday
Man United 3-0 Ipswich
Liverpool 3-2 Carlisle