Josh Harrop has been handed his full debut as Blues boss Paul Lambert makes five changes from the team which lost 2-1 at Peterborough a week ago.
Luke Matheson and Myles Kenlock return as the full-backs with Stephen Ward and Luke Chambers dropping to the bench. Luke Woolfenden and Mark McGuinness continue at centre-half with Tomas Holy in goal.
Flynn Downes skippers from the deeper midfield role with Andre Dozzell and debutant Harrop,, one of five loan players in the starting XI, ahead of him with Teddy Bishop and Alan Judge subs having started at London Road.
Troy Parrott is the lone central striker with Freddie Sears on the left and Luke Thomas on the right. James Norwood is on the bench.
Second-bottom Northampton make two changes from the team which lost 2-0 at home to Burton Albion on Saturday with Jack Sowerby and Fraser Horsfall replacing Ryan Watson and Cian Bolger.
Ipswich: Holy, Matheson, Woolfenden, McGuinness, Kenlock, Dozzell, Downes (c), Harrop, Thomas, Sears, Parrott. Subs: Cornell, Chambers, Ward, Bishop, Judge, Lankester, Norwood.
Northampton: Mitchell, Kioso, Horsfall, Jones, Mills (c), McWilliams, Sowerby, Morris, Hoskins, Marshall, Rose. Subs: Arnold, Bolger, Harriman, Watson, Ashley-Seal, Edmondson, Chukwuemeka. Referee: Darren Drysdale (Lincolnshire).