Jayden Stockley’s 26th minute goal has given Charlton a 1-0 half-time lead over the Blues at the Valley.
George Edmundson, Kane Vincent-Young, Lee Evans, Sone Aluko and Kyle Edwards returned to the Town side as interim manager John McGreal took charge of the Blues for the first time.
Edmundson, who missed out at the weekend with an achilles problem, joined Toto Nsiala at centre-half with Vincent-Young at right-back, Janoi Donacien moving to left-back for the first time for the Blues and Christian Walton in goal.
In midfield, Evans rejoined skipper Sam Morsy in the centre of midfield with Aluko on the right and Edwards on the left and Scott Fraser the number 10 behind former Charlton striker Macauley Bonne.
From the side which drew 0-0 with Barrow on Saturday, Conor Chaplin, Idris El Mizouni and Cameron Burgess were on the bench, while Bailey Clements and Kayden Jackson were left out of the 18.
Bersant Celina was again absent having suffered a knock in training at the end of last week, while young midfielder Cameron Humphreys kept his place on the bench having impressed as a sub on Saturday.
For Charlton, skipper Jason Pearce returned to their back three after a knee problem, while keeper Craig MacGillivray also came into the side for former Blues loanee Stephen Henderson, who started Friday’s 2-0 FA Cup victory at Gateshead.
Among those watching from the stands was former Waterford manager and one-time QPR midfielder Marc Bircham, who has been linked with the Blues’ management vacancy having worked as assistant boss at Arizona United five years ago, the club now known as Phoenix Rising, the club in which Town’s Three Lions are co-owners.
It’s believed he was at the game under his own steam rather than having been invited by the Blues.
Town, in their white and black away kit, started strongly with Aluko missing his kick when well placed after a ball from the left came in in the third minute.
The Addicks’ first chance came a minute later when one-time Blues target Conor Washington tried to catch Walton off his line but sent the ball into the 3,000-plus Town fans behind the goal.
On six, applause rippled around the ground in tribute to six-year-old Birmingham supporter Arthur Labinjo-Hughes, who was killed by his father and step-mother, with a number of players joining in ahead of a throw-in.
Keeper Walton confidently caught balls into the box from a corner and a free-kick and looked to throw out as quickly as he could - something he hadn’t done in previous games - but with Aluko and then Bonne unable to profit from it.
After Town’s bright start, Charlton had begun to gain the upper hand and on the quarter hour Ben Purrington’s free-kick from the left flashed across the Blues box but with Alex Gilbey unable to get a touch.
In the 24th minute, Diallang Jaiyesimi headed over the bar at the far post from Purrington’s cross.
And a minute later, the Addicks went in front. Washington burst into the box on the left - with Town arms raised for offside -cut in and hit a shot which Walton did well to save. However, the loose ball fell to Stockley, who slammed home.
Town protests continued and they looked to have a case but neither referee Christopher Sarginson nor his linesman showed any interest.
Donacien was shown the first yellow card of the game in the 29th minute for a foul on Gilbey.
Having gone behind, the Blues found themselves somewhat under the cosh with the home side visibly more confident having gone in front.
On the half hour, Stockley shot across the face of goal, Walton saved and the loose ball ran agonisingly behind Washington before being cleared.
Five minutes later, Elliot Lee sent Washington way but the Northern Ireland international found Nsiala in his way.
Town were showing little threat going forward. Aluko took too heavy a touch when breaking away down the right and the ball was put out for a throw.
On 41 Evans headed over from the Blues’ first corner of the game, taken by Aluko on the right, when he will feel he might have done better.
As the break approached Town began to get on top and in the final scheduled minute Fraser played a superb ball in from the left but which was just too far in front of Bonne for the striker to get in a shot.
Moments later, an Evans shot from the edge of the box was deflected out for a corner from which Nsiala nodded wide at the back post.
Soon after, the whistle confirmed the end of a half in which the Blues had started strongly before Charlton got on top and scored their goal with Town looking to have a strong case that it was offside.
The Addicks might have added to their lead having been well on top following the goal but the Blues came back into it in the minutes before the break. However, Town will have to show more in the second half if they’re to avoid falling to their first defeat at the Valley since 2008.
Charlton: MacGillivray, Clare, Pearce (c), Famewo, Jaiyesimi, Gilbey, Dobson, Lee, Purrington, Stockley, Washington. Subs: Henderson, Elerewe, Souaré, Watson, Kirk, Leko, Davison.
Town: Walton, Vincent-Young, Nsiala, Edmundson, Donacien, Evans, Morsy (c), Aluko, Fraser, Edwards, Bonne. Subs: Hladky, Burgess, Penney, El Mizouni, Humphreys, Chaplin, Pigott. Referee: Christopher Sarginson (Staffordshire).