An injured quadriceps will keep Gurley from playing, NFL Network's Omar Ruiz reported on Saturday.
ESPN's Lindsey Thiry first reported the news.
Gurley was designated as doubtful on Friday, so his out status was expected.
Gurley will miss his first game since Week 17 of last year's regular season.
Gurley's workload had already been toned down with just 78 touches through the first five weeks, as he's gained 270 yards on 64 carries with 68 yards on 14 receptions.
Brown has shown promise in his opportunities this season, having averaged 4.4 yards per carry on 26 attempts with two touchdowns. Henderson should get his first substantial work as he's had just one touch.