The centre-back is one of nine changes made by Roy Hodgson as he attempts to evaluate his Eagles squad, with only Andros Townsend and Jeffrey Schlupp remaining from the side that lost to Southampton on the weekend.
Sakho lines up alongside fellow recent injury-victim James Tomkins in the heart of defence, with Patrick van Aanholt and Martin Kelly in the full-back positions. Luka Milivojevic and Jairo Riedewald are in defensive midfield, with Townsend and Schlupp on the flanks, supplying a front line of Chung-yong Lee and Bakary Sako.
Captain for the night is Julian Speroni on the occasion of his 392nd appearance, and included on the Eagles bench is Pape Souare, who could get his first first-team minutes in over a year after recovering from his injuries sustained in a car accident 12 months ago.
Huddersfield also make nine changes to the team that drew 1-1 with Leicester City on Saturday, with Elias Kachunga expected to lead the attack.
Palace: Speroni, Kelly, Tomkins, Sakho, Van Aanholt, Townsend, Riedewald, Milivojevic, Schlupp, Lee, Sako. Subs: Hennessey, Souare, Ward, Delaney, Mutch, Cabaye, Benteke.
Huddersfield: Coleman, Malone, Hadergjonaj, Hefele, Cranie, Billing, Hogg, Lolley, Ince, Van la Parra, Kachunga. Subs: Lossl, Smith, Lowe, Jorgensen, Whitehead, Mooy, Sabiri.