In the first round, relegation-threatened Cambridge won 1-0 away to National League side Woking, while Wigan travelled to League Two Carlisle United and won 2-0.
Match preview
Cambridge are currently third-last in League One with 13 points and occupy 22nd place - one of the division's four relegation spots.
Monk's side are winless in their last four league games, drawing their most-recent three, and were on the receiving end of a 6-1 thrashing at the hands of mid-table Peterborough United on November 9.
Last time out, an 89th-minute header from Sullay Kaikai rescued a point for a resilient Cambridge, who played with 10 men against Bolton Wanderers after Jubril Okedina's red card early in the second half.
Despite their lacklustre recent form, The U's are not yet hopeless given they are just three points from escaping the relegation zone, have lost just one of their last nine games and, prior to their defeat against Peterborough, managed to record a five-game winning streak in all competitions.
That being said, only Stevenage have scored fewer goals than Cambridge in the league this season, and they will likely need to improve their output if they are to remain in the division.
Though they were eliminated from the League Cup by Championship side Queens Park Rangers in August, Cambridge's last two wins have been in cup competitions, and Monk's team will be hoping to inspire their 2024-25 campaign with a solid cup run.
Cambridge beat Chelsea U21s in the EFL Trophy on November 5 and Woking in the FA Cup on November 2, and have the opportunity to get back to winning ways this weekend against a Wigan side they beat 2-0 in October.
Shaun Maloney's Wigan are 15th in League One, seven points ahead of Cambridge after 16 matches, and will be looking to make it four wins on the bounce when they face The U's this weekend.
In contrast to Cambridge, Wigan have won or progressed from four of their last five matches in all competitions, and their only loss in that period was a narrow 1-0 defeat against top of the table Wycombe Wanderers.
Last time out, the Latics beat Northampton Town 2-1 on November 26 after two first-half goals from Thelo Aasgaard and Jonny Smith put them in command of the game.
Impressively, Wigan have the second-best defensive record in League One this season having conceded just 13 goals so far, and this defensive solidity could be a problem for Cambridge's struggling attack.
On the other hand, Maloney's side have only managed to score one more goal than Saturday's opponents in League One, and the team's ability to keep a clean sheet will be key to their chances of progressing to the third round of the FA Cup this weekend.
Cambridge United FA Cup form:
W
Cambridge United form (all competitions):
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W
L
D
D
D
Wigan Athletic FA Cup form:
W
Wigan Athletic form (all competitions):
D
W
L
W
W
W
Team News
Cambridge will be without defender Okedina after his red card against Bolton, and Monk could start Zeno Ibsen Rossi, who was subbed on to fill in during that game.
Likewise, Kaikai could keep his place in the XI after he managed to rescue a point for Cambridge in their last outing.
As for the visitors, Maloney has stated that he will be selecting his strongest available team due to the potential reward of a major tie against a Premier League side in the third round of the FA Cup.
With this in mind, expect goalkeeper Sam Tickle to be shielded by captain Jason Kerr and Will Aimson, Aasgaard to feature in midfield again after his goal against Northampton and Nottingham Forest loanee Dale Taylor to lead the forward line.
Cambridge United possible starting lineup:
Reyes; Rossi, Morrison, Andrew; Bennett, Cousins, Smith, Brophy; KaiKai, Loft, Njoku
Wigan Athletic possible starting lineup:
Tickle; Sibbick, Kerr, Aimson, Sessegnon; M. Smith, J. Smith, Weir, Aasgaard, Thomas; Taylor
We say: Cambridge United 1-2 Wigan Athletic
Both sides will be keen to reach the third round of the FA Cup, when Premier League teams enter the competition, so expect a close tie between two of the lowest-scoring sides in League One.