Frank Lampard makes seven changes from the game at Leicester with both Tammy Abraham and Timo Werner starting.
There are also places for Christian Pulisic and Hakim Ziyech in a strong line-up.
Mason Mount is captain for the first time with Billy Gilmour given a start alongside him.
In defence, Andreas Christensen plays for the first time in 2021.
Luton start with their top scorer this season, James Collins, on the bench.
Chelsea Kepa; James, Christensen, Zouma, Emerson; Gilmour, Mount (c); Ziyech, Werner, Pulisic; Abraham.Substitutes Caballero, Azpilicueta, Rudiger, Chilwell, Jorginho, Kovacic, Havertz, Hudson-Odoi, Giroud.
Luton Sluga, Bree, Bradley (c), Lockyer, Naismith, Tunnicliffe, Rea, Mpanza, Clark, Cornick, Dewsbury-Hall.
Subs Shea, Potts, Berry, Hylton, Lee, Moncur, Collins, LuaLua, Nombe.
The referee is David Coote.
Chelsea are hoping to progress to the FA Cup fifth round for the 23rd time in 26 attempts.
Since our home defeat to Bayern Munich last February, Frank Lampard’s side have only lost two of our 20 matches at Stamford Bridge, winning 13 of them.