The 29-year-old scored on his most recent Three Lions appearance against Wales last month.
But he has been omitted by boss Thomas Tuchel for qualifiers against Serbia and Albania as he struggles for form at club level.
Watkins, Villa’s all-time top scorer in the Premier League, has netted just one goal in 15 appearances this season.
His Villa team-mates Ezri Konsa and Morgan Rogers have been included in the squad, with Tuchel also recalling Real Madrid midfielder Jude Bellingham.
Manchester City’s Phil Foden and Crystal Palace’s Adam Wharton are in the 25-man group, while Bournemouth midfielder Alex Scott has been handed a first senior call-up.