The 26-year-old missed Villa's 3-2 opening day defeat at Watford with bruising on his left knee and the same issue will keep him out against the Magpies.
Watkins was the club's top scorer in the Premier League, scoring 14 goals. Villa boss Dean Smith, who insists the injury is not long-term, is hopeful Watkins will be fit to face Brentford on August 28.
Danny Ings will again start up front in his absence while summer signing Leon Bailey could make his first start, after impressing off the bench at Vicarage Road.
But fellow winger Bertrand Traore is facing around three weeks out with a hamstring injury sustained earlier this week during a behind closed doors friendly at Liverpool.
Boss Dean Smith is hopeful the Burkina Faso will be ready for a return to action after the September international break.