The winger represents the sole change to the side which won 1-0 against Bristol Rovers on Saturday, with James Bolton replacing him.
Potentially it means Marcus Harness will go to left wing-back, with Callum Johnson switched to the right.
That would then leave Bolton partnering Sean Raggett and Rasmus Nicolaisen in a back three for a match the Blues can ill afford to lose as they chase a play-off spot.
However, there is no place for Lee Brown, despite Danny Cowley having revealed he was available again following a hamstring injury.
Williams takes his place on the bench in an 18-man squad unchanged from their weekend win which lifted them into seventh spot.
Pompey: MacGillivray, Bolton, Raggett, Nicolaisen, Johnson, Harness, Close, Naylor, Curtis, Byers, Marquis.
Subs: Ward, Williams, White, Stanley, Downing, Cannon, Daniels.