Head coach Rex Ryan announced the decisions Friday. He told reporters Wednesday that the duo were likely to miss the game.
McCoy, acquired from Philadelphia in an off-season trade suffered a hamstring injury in training camp and has battled the injury since, rushing for 146 yards and no touchdowns in Buffalo's first three games. Rookie running back Karlos Williams should carry the rushing load Sunday.
Watkins was diagnosed with a mid calf strain during Buffalo's 41–14 win over the Dolphins on Sunday and was day-to-day throughout the week. Last year's first-round pick has seven catches for 99 yards and a touchdown through three games.
The Bills (2–1) will take on the Giants in Buffalo at 1 p.m. ET Sunday.
- Jeremy Woo