Barnet produced a giant-killing at Portsmouth, Sven Goran Eriksson's Leicester eventually proved too strong for Rotherham, and Marvin Emnes inspired Middlesbrough at Walsall in the Carling Cup first round.
Southampton knocked out Torquay, Peterborough required extra-time against Stevenage, Preston staged a spectacular, late turnaround against Crewe to avoid more misery, while Millwall overcame Plymouth.
League Two Barnet stunned Steve Cotterill's Portsmouth at Fratton Park as the former Premier League club were knocked out courtesy of Mark Hughes' solitary goal in the 30th minute.
Sven Goran Eriksson's Leicester overcame new-boy Matt Mills' early own-goal to progress into the second round with a 4-1 win over Rotherham courtesy of a Jeffery Schlupp hat-trick at a deserted Don Valley Stadium.
After signing a contract extension last week, Emnes celebrated in style as his treble helped Middlesbrough to a 3-0 win at Walsall, who never recovered from Adam Chambers' 12th minute red card.
Lee Tomlin's penalty in the final seconds of extra-time gave Darren Ferguson's Peterborough a nervy 4-3 win at Stevenage.
On the back of a heavy home defeat against Colchester in their League One season-opener, Phil Brown's Preston seemed set for another day to forget before Neil Mellor and Iain Hume both scored in the final six minutes to secure a dramatic 3-2 win over League Two Crewe.
Debutant Dany N'Guessan's 14th minute goal proved the difference between Plymouth and Millwall, with the Championship side picking up a 1-0 win.
Lee Clark's Huddersfield came from a goal down as a brace from Lee Novak helped them to a 4-2 win at Port Vale.
Southampton, who impressed against Leeds on Saturday, were made to work hard against fellow South Coast outfit Torquay, but the League Two team were ultimately defeated 4-1 at St Mary's.
Rochdale and Chesterfield drew 1-1 after 90 minutes but Ashley Grimes' second goal of the game in a seesaw period of extra-time secured the home side a 3-2 win.
Southend versus Leyton Orient could not be separated after 120 minutes following a 1-1 draw but Orient won 4-3 on penalties.
Wycombe and Colchester drew 3-3 after extra-time at Adams Park before the former won 5-4 on spot-kicks.