These two clubs shared the same division as recently as 2022, but are now three leagues apart, thanks largely to Ipswich's meteoric rise.
Match preview
It has been a baptism of fire for Ipswich on their return to the top flight, as the Tractor Boys were handed about as tough a start as physically possible.
Hosting Liverpool on the opening day was followed by a trip to champions Manchester City, both of which, as expected, ended in defeat.
Sammie Szmodics gave the Ipswich faithful a moment that will live long in the memory when he put them in front at the Etihad on Saturday, but a clinical Erling Haaland combined with a shaky debut from goalkeeper Arijanet Muric saw City win 4-1.
Hosting Fulham at Portman Road this weekend will be another difficult ask given the start Marco Silva's side have made, so that places plenty of importance on Ipswich getting their season up and running in the cup this midweek.
It is testament to the job Kieran McKenna has done at the club that these two clubs met in League One just over two years ago, as the gulf between the two is now astronomical.
There has been a more recent meeting between the sides too, as Ipswich won 3-1 here at Plough Lane back in January in the third round of the FA Cup.
The following round saw Ipswich dumped out by non-league Maidstone United though, so avoiding another giant killing will be the main aim here.
Ipswich have enjoyed little success in this competition in recent seasons though, as eight of the previous 13 campaigns saw them lose in round one - a stage they were given a bye in this season for being a Premier League club.
After almost slipping out of the EFL in 2022-23, Wimbledon will now have their sights on a return to League One following a respectable mid-table finish last season.
The club has made a strong start to the new campaign too, with four wins in five games across three competitions.
Only two points separate the entire top half in League Two, and Wimbledon are in the middle of that pack on six points, with defeat to EFL debutants Bromley the only blemish so far.
Bromley were the side Wimbledon defeated to reach the second round though, just days before their league defeat earlier this month.
Wins over Colchester United and Cheltenham Town in the league and Wycombe Wanderers in the EFL Trophy mean it has been a largely promising start for Johnnie Jackson's men.
This is just the fourth time Wimbledon have made it beyond the first round, but it is another difficult second round fixture for the Dons, as they became just the second side in almost three decades to meet Chelsea at that stage last season.
AFC Wimbledon EFL Cup form:
W
AFC Wimbledon form (all competitions):
Ipswich Town form (all competitions):
Team News
New Ipswich signing Kalvin Phillips picked up a minor knock last week, but would have been ineligible to face his parent club Man City anyway.
Phillips joined Wes Burns, Nathan Broadhead, George Hirst and Janoi Donacien on the sidelines, with those four set to remain out.
After an unconvincing debut in goal, Muric's place may be under threat by Christian Walton, who started on the opening day against Liverpool, while Jens Cajuste, Dara O'Shea and Jack Clarke could all be in line for their first appearances at the club.
Wimbledon wing-back Huseyin Biler missed out altogether in the win over Cheltenham after being forced off in the dying stages of their EFL Trophy win over Wycombe last midweek.
Josh Neufville was the man to come in to replace Biler at the weekend, and may need to deputise again if he is unable to get over that knock in time.
Defender Isaac Ogundere dropped to bench at the weekend, as new signing Riley Harbottle has arrived from Hibernian and hit the ground running with two fine performances so far in back-to-back wins.
AFC Wimbledon possible starting lineup:
Goodman; Harbottle, Lewis, Johnson; Neufville, Smith, Reeves, Hippolyte, Furlong; Pigott, Bugiel
Ipswich Town possible starting lineup:
Muric; Johnson, O'Shea, Woolfenden, Greaves, Davis; Clarke, Cajuste, Morsy, Chaplin; Al-Hamadi
We say: AFC Wimbledon 0-2 Ipswich Town
While it has been a tough start at the top table for Ipswich, League Two opposition should give them the opportunity to get their season off and running, even if McKenna opts to change some personnel.