On the back of Sunday's 2-0 defeat at Nottingham Forest, head coach Unai Emery has opted to freshen up his side as Villa attempt to move six points clear of last season's semi-finalists with two games remaining.
The most notable alterations come in defence with Diego Carlos and Clement Lenglet lining up in the middle of the backline, Ezri Konsa seemingly moving to right-back.
Youri Tielemans, as expected, returns in central midfield having continued to miss out on Premier League starts, while Leon Bailey will feature on the flank.
Matty Cash, Pau Torres, Douglas Luiz and Nicolo Zaniolo have all dropped down to the substitutes' bench.
Alex Moreno will hope to make his first appearance of the season as a replacement, while Jhon Duran could make just his second outing for over a month.
Meanwhile, AZ boss Pascal Jansen has made two changes from the team that started the 1-1 draw at Excelsior at the weekend.
Ibrahim Sadiq and Ruben van Bommel will start in wide areas with Jens Odgaard and Myron van Brederode only being kept in reserve.
Aston Villa: Martinez; Konsa, Carlos, Lenglet, Digne; McGinn, Kamara, Tielemans, Bailey; Diaby; Watkins
Subs: Olsen, Marschall, Cash, Luiz, Traore, Torres, Moreno, Chambers, Zaniolo, Duran, Dendoncker
AZ Alkmaar: Ryan; Sugawara, Bazoer, Martins Indi, Moller Wolfe; Clasie, De Wit, Nijnans; Sadiq, Pavlidis, Van Bommel
Subs: Verhulst, Deen, Penetra, Dantas, Odgaard, Mihailovic, Van Brederode, Poku, Dekker, Goudmijn, Kasius, Goes