Tomiyasu and Saliba were both forced off in the first half of the Gunners' Europa League last-16 second leg with Sporting Lisbon, picking up knee and back issues respectively.
The former was seen leaving the stadium on crutches, while reports have claimed that Saliba could now be facing a few weeks out, as Holding unsurprisingly comes in for his first Premier League start of the season - 18-year-old Reuell Walters is named on the bench.
Ben White was always expected to return for Tomiyasu either way, while Oleksandr Zinchenko, Gabriel Magalhaes and Aaron Ramsdale retain their spots at the back despite a gruelling 120 minutes on Thursday.
Granit Xhaka, Martin Odegaard and Thomas Partey form a first-choice engine room, as Fabio Vieira and Jorginho are relegated to the bench, while Bukayo Saka displaces Reiss Nelson up top.
Having made his first start since recovering from knee surgery in midweek, Gabriel Jesus drops to the bench, allowing Leandro Trossard to come back in alongside Gabriel Martinelli.
As for managerless Crystal Palace, academy product Joe Whitworth continues in goal with Vicente Guaita and Sam Johnstone absent, while Arsenal loanee Albert Sambi Lokonga is replaced by Luka Milivojevic.
Arsenal starting lineup: Ramsdale; White, Holding, Gabriel, Zinchenko; Partey, Xhaka, Odegaard; Saka, Trossard, Martinelli
Subs: Turner, Tierney, Walters, Kiwior, Jorginho, Vieira, Smith Rowe, Nelson, Jesus
Crystal Palace starting lineup: Whitworth; Ward, Andersen, Guehi, Mitchell; Milivojevic, Doucoure, Schlupp; Olise, Edouard, Zaha
Subs: Goodman, Tomkins, Ayew, Eze, Mateta, Clyne, Hughes, Richards, Ahamada