Andre Villas-Boas has swapped Steven Caulker and Michael Dawson for Kyle Naughton and William Gallas for Tottenham Hotspur's trip to Villa Park.
Jan Vertonghen will move to central defence to partner Gallas, with Naughton taking up a familiar left-back role.
Jermain Defoe and Emmanuel Adebayor continue in attack despite failing to find a way past Stoke City last weekend.
Aston Villa boss Paul Lambert has dropped Andre Weimann, Barry Bannan and Eric Licahj from the team which were thrashed 8-0 by Chelsea on Sunday.
In come Karim El Ahmadi, Joe Bennett and Fabian Delph for the home side.
Villa: Guzan, Lowton, Herd, Clark, Baker, Bennett, Westwood, El Ahmadi, Delph, Holman, Benteke
Spurs: Lloris, Walker, Gallas, Vertonghen, Naughton, Lennon, Dembele, Sandro, Bale, Defoe, Adebayor