Gronk was limited in practice all week after injuring his hamstring a fortnight ago.
The news is a huge blow to quarterback Jimmy Garoppolo, starting his first career game in place of the suspended Brady.
Gronk is the NFL's most dynamic target when healthy. The tight end's combination of size and speed makes him a mismatch against linebackers, safeties and corners.
Since entering the NFL in 2010, Gronkowski has more receiving yards (5,555) and receiving touchdowns (65) than any other tight end. Gronk also leads the NFL in touchdowns since 2010 (66, including one rushing TD).
The 27-year-old target has missed 15 games in his career due to injury. In those games, however, the Pats had a Hall of Famer at quarterback.
With Gronk out, New England will turn to newly acquired Martellus Bennett as the primary pass-catching tight end.
Hamstrings are fickle beasts, so it's possible the Patriots didn't want to tempt the football gods and risk losing their top target for a longer stretch.
One thing is certain, without Gronk, Jimmy G's difficult journey to the desert became much tougher.