The Saints fly-half has previously played for the Saxons, but should he enter the fray in Buenos Aires this weekend he will win his first full international cap.
Myler gets his chance after centre Billy Twelvetrees was called up by the Lions as an injury replacement.
The Northampton No.10 is joined in England’s matchday squad by Saints team-mates Lee Dickson, Ben Foden, Courtney Lawes and skipper Tom Wood.
Dickson and Wood keep their starting spots following the impressive 32-3 win in the first Test against the Pumas in Salta last Saturday.
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Lawes and Foden came off the bench in that game, with the lock being sin-binned with 11 minutes to go.
England: Brown; Wade, Joseph, Eastmond, Yarde; Burns, Dickson; Marler, Webber, Wilson, Launchbury, Attwood, Wood (c), Kvesic, Morgan.
Replacements: Paice, Doran-Jones, Thomas, Lawes, Vunipola, Wigglesworth, Myler, Foden.