Beattie, the 20-year-old Glasgow Warriors number eight, and Edinburgh centre Dewey, 23, will start at Murrayfield on Saturday.
Stand-off Phil Godman and tight-head prop Euan Murray will also make their first Scotland starts, after winning caps from the bench.
Uncapped forwards David Callam and Jim Hamilton are on the bench - and if both are introduced the number of players to be capped by Scotland will reach 1,000.
Scotland head coach Frank Hadden said: "There were a number of players I was particularly keen to see playing at this level - Godman, Dewey, Beattie, Euan Murray and Hamilton - and on that basis I've looked at the balance of the rest of the side and how best these players can be accommodated.
"That said, what this match is about is building on the progress we made last season and fielding a winning Scotland team.
"I'm not sacrificing our goal of winning a fourth successive game at Murrayfield for the first time in 11 years simply to introduce new players."
Hadden believes consistent displays in the Magners League have earned the new caps their chance.
But he added: "I'm having a look to see how they fare.
"I know we have very good players in their positions and I expect Rob and Johnnie to rise to that.
"If they want to see themselves as contenders for the Scotland team they have to show me that desire on Saturday."
Hadden has signalled his intent to deploy replacements Allan Jacobsen and Craig Smith at some stage as competition for front-row berths intensifies.
Scotland also face home fixtures against Pacific Islanders and Australia in this month's Bank of Scotland Corporate autumn Test series.