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.
Ian Porterfield and David Pleat were in charge the last time the sides met at Stamford Bridge, in August 1991 in the old First Division. The Blues ran out 4-1 winners with our goals coming from Graeme Le Saux, Andy Townsend, Kerry Dixon and Dennis Wise.
Luton’s last victory at the Bridge was in September 1986, also in the First Division.
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.