Prosise was helped off the field after a 2-yard run midway through the second quarter. A Notre Dame spokesman confirmed that he would not return but would not elaborate on the injury.
Prosise ran eight times for 57 yards in the game. That put him over 1,000 yards for the season. He reached the milestone on his 150th carry of the season - the second-fastest in school history. Reggie Brooks needed 120 plays to reach 1,000 yards in 1992.
No. 5 Notre Dame played a home game at Fenway Park as part of its Shamrock Series.