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Holders Peterborough United went out and Harrogate Town belied their status as the lowest-placed team still in this season's Vertu Trophy among 14 ties in the last 32 on Tuesday.
After an uneventful first half away to League Two promotion contenders Swindon Town, League One strugglers Peterborough dominated the second period but conceded the only goal of the game when Robins captain Ollie Clarke slotted in the 88th-minute winner.
Harrogate are a point from safety after taking two points from eight league matches since their last League Two win on September 27, but Jack Muldoon scored the pick of the goals as Simon Weaver's side moved 3-0 ahead after 17 minutes at the Exercise Stadium against League One visitors Blackpool.
Town held off a comeback and scored again late on through Muldoon in a 4-2 win to ensure they have taken scalps throughout their perfect four-match run in this season's trophy, beating League One opponents Mansfield Town and Huddersfield Town and Newcastle United Under-21s to top their group.
League One bottom side Port Vale earned the joint-largest win of the night with a 5-0 home win over Barnsley, helped by two Ruari Paton goals inside the opening eight minutes and a splendid first goal of the season for New Zealand forward Ben Waine.
Rotherham United also prevailed by five at Salford City, where the League Two hosts took the lead and made the scoreline 2-2 before a Josh Benson hat-trick inside 17 minutes - including a lob from near the halfway line - helped the Millers win 7-2.
AFC Wimbledon arrived as the unseeded side at League One leaders Cardiff City and proceeded to hand the Bluebirds a shock 5-1 home thrashing, including four goals for 20-year-old academy graduate Aron Sasu and a goal and assist for Omar Bugiel.
Bristol Rovers have lost their last eight matches in League Two and had less than 30% of possession at home to Cambridge United, but the Pirates overcame conceding a 94th-minute equaliser in a 2-2 draw to secure their second win on penalties in this season's competition, Kamil Conteh scoring the decisive spot kick.
Lorent Tolaj was sent off for violent conduct in Plymouth Argyle's defeat at Northampton on Saturday and the striker went some way towards atoning for his indiscretion by backheeling the winner in the 93rd minute of their 1-0 win at Leyton Orient.
Veteran striker Billy Sharp opened the scoring from 30 yards and finished on two goals and two assists - also setting up Damola Ajayi and Luke Molyneux either side of a Jack Senior goal - as Doncaster Rovers beat Chesterfield 5-1.
Former Norway U21 forward Lasse Nordas scored twice and set up another for Shayden Morris as League One promotion hopefuls Luton Town scored three first-half goals as part of a 4-0 home win over Exeter City, Zack Nelson curling in the fourth after the break.
Two strikes inside 10 first-half minutes by on-loan Toulouse winger Ibrahim Cissoko put Bolton Wanderers on their way to a 3-0 home win over Bradford City, with Marcus Forss - borrowed from Middlesbrough - hitting the third during the second half.
League Two leaders Walsall looked to be going out when Carl Piergianni headed hosts Stevenage in front in the 57th minute of their tie, only for on-loan Rico Richards to score his first goals since March with two finishes inside 10 minutes as the Saddlers won 2-1.
Wycombe Wanderers will not be repeating their run to the final of the 2023-24 competition after losing 2-0 at Northampton Town, whose first-half goals came through a counter-attack completed by Kyle Edwards and Tyrese Fornah's finish from the edge of the box.
Fleetwood Town won twice on penalties during an unbeaten group stage but there was no such drama in their 3-0 win at Tranmere Rovers, where Patrick Brough's own goal and strikes by Ronan Coughlan and Mark Helm sent Pete Wild's side through.
Murray Wallace marked his first Huddersfield Town appearance since September by setting up Joe Taylor's second-half opener at Lincoln City, putting the Terriers on course for a victory they sealed through Wallace's 90th-minute header in a 2-0 win.
Bolton Wanderers 3-0 Bradford City
Bristol Rovers 2-2 Cambridge United (Bristol Rovers win 4-2 on penalties)
Cardiff City 1-5 AFC Wimbledon
Doncaster Rovers 5-1 Chesterfield
Harrogate Town 4-2 Blackpool
Leyton Orient 0-1 Plymouth Argyle
Lincoln City 0-2 Huddersfield Town
Luton Town 4-0 Exeter City
Northampton Town 2-0 Wycombe Wanderers
Port Vale 5-0 Barnsley
Salford City 2-7 Rotherham United
Stevenage 1-2 Walsall
Tranmere Rovers 0-3 Fleetwood Town
Swindon Town 1-0 Peterborough United
