Saracens pair Farrell and Barritt will become England's first uncapped centre pairing since 2002 - and only the second since 1969 - while Dowson starts at number eight.
Interim head coach Stuart Lancaster has named a total of eight uncapped players in his 22-man squad for the trip to Murrayfield.
Wasps hooker Rob Webber, Leicester lock Geoff Parling, Scarlets number eight Ben Morgan, Northampton scrum-half Lee Dickson and Harlequins centre Jordan Turner-Hall are all primed to make their debuts from the bench.
Lancaster's starting line-up boasts just 236 Test caps, including Lions appearances, compared to Scotland's 501. The Scottish pack alone has more international experience than England.
Saracens fly-half Charlie Hodgson is the most experienced player in the England line-up with 36 caps, but he will be making his first Test start in four years.
Seven of England's starting XV go into the game with 10 caps or fewer, while Chris Robshaw will captain England in only his second Test appearance.
Saracens lock Mouritz Botha will be making his first international start following a debut off the bench last August.
"We have been impressed with how the whole group has come together in the last 10 days and we have done a lot of work on and off the field," Lancaster said.
"Now is the time to turn all that into a performance against Scotland that we can all be proud of. It is a massive challenge - Murrayfield, the first game of the Six Nations - but one we are relishing."
The England team features 10 changes from the side that beat Scotland in the World Cup last October and nine from the quarter-final defeat to France.
Jonny Wilkinson, Steve Thompson and Lewis Moody have retired, while England are without the injured trio of Toby Flood, Courtney Lawes and Manu Tuilagi.
England team to play Scotland in the at Murrayfield on Saturday (5pm):
B Foden (Northampton); C Ashton (Northampton), B Barritt (Saracens), O Farrell (Saracens), D Strettle (Saracens); C Hodgson (Saracens), B Youngs (Leicester); A Corbisiero (London Irish), D Hartley (Northampton), D Cole (Leicester), M Botha (Saracens), T Palmer (Stade Francais), T Croft (Leicester), C Robshaw (Harlequins, captain), P Dowson (Northampton).
Replacements: R Webber (Wasps), M Stevens (Saracens), G Parling (Leicester), B Morgan (Scarlets), L Dickson (Northampton), J Turner-Hall (Harlequins), M Brown (Harlequins).
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