Wycombe Wanderers were the only League 2 side to knock out higher league opposition. The Chairboys beat Colchester United 2-0 in the Southern section thanks to two second half goals.
Kevin Betsy broke the deadlock after 75 minutes and seven minutes later Scott Davies sealed the win.
Of the all League 1 ties, 11th placed Huddersfield Town held off a late Peterborough United fight back to knock out the side currently second in the table. This was the pick of the results in the Northern section given that the Terriers, who had already lost 4-2 to Posh in the league, went into the game on the back of three straight defeats.
Graham Carey gave the home side the early advantage after six minutes and Anthony Pilkington then struck twice to give them a comfortable 3-0 lead midway through the half.
Posh began their comeback six minutes into the second period through Aaron Mclean and Mark Little headed a second Posh goal with nine minutes to go but it was too late to grab a third and force the match into penalties.
HAPPY TRIPS HOME
Southend United and Crewe Alexandra both enjoyed victories on the road over fellow League 2 outfits.
The Shrimpers were 3-1 victors at Underhill over Barnet. Matthew Paterson scored a goal in each half, the second five minutes after the visitors had Bilel Mohsni dismissed for violent conduct.
With 11 minutes to go the Bees pulled one back through Mark Marshall but the ten men held on and with five minutes to go Louie Soares scored a third to secure their passage into the next round.
In a bizarre game at Macclesfield Town, three of the opening four goals were own goals with the other coming from the spot.
Crewe defender Patrick Ada twice put through his own net in the opening half hour. A Colin Daniel own goal after four minutes had given the Alex the lead but the first of Ada's two errors drew Macclesfield level. Lee Bell then scored from the spot to restore the away team's advantage, if only for a minute, before Ada disastrously struck again.
Two minutes into the second half David Artell gave Crewe the lead for the third time and 11 minutes after Joel Grant added a fourth to wrap up a 4-2 away win.
With six away teams winning, the pick of the other results arrived at Edgar Street where Hereford United's woes continued when they were comfortably beaten 3-0 by Exeter City.
A Daniel Nardiello penalty after 12 minutes and a John O'Flynn goal early in the second half set them up, Richard Duffy added a third in injury time to give the Grecians the biggest victory on the night.
AT THE DEATH
Brentford knocked out their London rivals Leyton Orient on penalties to progress to the next round.
The sides finished goalless after 90 minutes but the teams had no trouble finding the net from twelve yards. Nine were scored before Richard Lee became the Bees hero, just as he was in their Carling Cup victory over Everton recently, saving Matthew Spring's spot kick.
Bury and Shrewsbury Town also couldn't be separated during normal time and after a 0-0 draw the two sides traded blows from the spot. The first 10 penalties were despatched and when the shoot out went to sudden death Shakers goalkeeper Cameron Belford stepped up to grab the headlines. First he saved Daniel O'Donnell's penalty before thumping home his own to give Bury a 6-5 spot kick success.
Last season's finalists Carlisle United survived a scare against League 2 leaders Port Vale to comeback and eventually knock them out 4-3 on penalties.
An own goal from Carlisle's Oliver Norwood gave the Valiants the lead three minutes before half-time and when Marc Richards added a second after 64 minutes it all looked good for Micky Adams side.
Carlisle hit back with two goals in five minutes to take it to a shoot out. James Chester pulled one back for the home side 12 minutes later and Jason Price shortly afterwards to make it 2-2.
Bristol Rovers match with Aldershot Town looked set to become the fourth game to be settled on penalties when a last minute goal settled the tie.
Will Hoskins popped up to net from close range at the death to send the Gas Heads through.