Rooney has not played since last season, missing all of United's pre-season friendlies and the Community Shield curtain-raiser with Wigan last weekend.
Midfielder Jack Wilshere is also poised to start along with Arsenal team-mate Theo Walcott, while Liverpool defender Glen Johnson misses out along with Manchester United's Michael Carrick.
Celtic midfielders Scott Brown and James Forrest will start for Scotland, along with new Hull City goalkeeper Allan McGregor.
The match will be the first between the countries since 1999, when a Don Hutchinson goal gave Scotland a 1-0 win at Wembley.
England team: Hart, Walker, Jagielka, Cahill, Baines, Gerrard, Wilshere, Walcott, Rooney, Cleverley, Welbeck.
Scotland team: McGregor, Hutton, Whittaker, Hanley, Martin, Brown, Forrest, Snodgrass, Maloney, Morrison, Miller.