With Arsenal 10 points off the top four heading to the Riverside Stadium, Wenger has elected to mimic the three-man back line put to good use by rivals Chelsea and Tottenham this season.
Laurent Koscielny and Petr Cech return to bolster Arsenal's defensive strength, while Rob Holding starts in the back line as the Gunners go 3-4-2-1 against Boro.
It is the first time since 1997 that Wenger has selected three at the back, with Alex Oxlade-Chamberlain and Nacho Monreal at wing-back with Mesut Ozil and Alexis Sanchez supporting Olivier Giroud in attack.
MiddlesbroughXI: Guzan, Barragan, Ayala, Gibson, Da Silva, Clayton, de Roon, Leadbitter, Ramirez, Negredo, Downing
Subs: Konstantopoulos, Friend, Bernardo, Bamford, Gestede, Forshaw, Traore
Arsenal XI: Cech, Gabriel, Koscielny, Holding, Oxlade-Chamberlain, Ramsey, Xhaka, Monreal, Ozil, Sanchez, Giroud
Subs: Gibbs, Walcott, Iwobi, Bellerin, Martinez, Coquelin, Elneny
Referee: Anthony Taylor