As he indicated yesterday, Thomas Tuchel hands starts to Kepa Arrizabalaga, N'Golo Kante, Hakim Ziyech and Billy Gilmour.
There is also a first start under the new boss for Kurt Zouma who will play alongside Andreas Christensen at the heart of the defence. Emerson Palmieri and Marcos Alonso are also selected.
Tammy Abraham leads the attack with Christian Pulisic and Callum Hudson-Odoi in the line-up.
Two Academy midfielders, 19-year-old Tino Anjorin and 18-year-old Lewis Bate, who was an unused sub at Sheffield United last season, are among the subs.
Barnsley have former Chelsea Academy player Brad Collins in goal, as they did for our 6-0 Carabao Cup win against them earlier in the season.
Chelsea Kepa; Christensen, Zouma, Emerson; Hudson-Odoi, Kante (c), Gilmour, Alonso; Ziyech, Abraham, Pulisic.
Subs Caballero, Azplicueta, James, Rudiger, Chilwell, Kovacic, Bate, Anjorin, Giroud.
Barnsley Collins; Brittain, Sibbick, Andersen; Helik, Kane, Mowatt (c), Styles; Woodrow, Chaplin, Adeboyejo.
Subs Walton, Sollbauer, Moon, Oduor, Williams, Dike, Frieser, Palmer, Thompson.
The referee is Martin Atkinson
Chelsea have progressed from 52 of our last 54 FA Cup ties against sides from a lower division, only losing against Barnsley in 2008 and Bradford City in 2015.