Florida State took an 11-point halftime lead and surged 23 points in front 7 minutes deep in the second period. With the Seminoles defending every shot, Notre Dame made only 31 percent of its field-goal attempts.
The surprisingly one-sided victory put the 10th-seeded Seminoles in the Southwest Region semifinals in San Antonio, where they will take on No. 11 seed Virginia Commonwealth.
The Southwest Region semifinals will also feature a No. 12 seed in Richmond, which will meet top-seeded Kansas.
Florida State became one of three teams from the Atlantic Coast Conference to reach the Sweet 16, more than any other league. The Seminoles have joined North Carolina and Duke in giving the ACC a tournament-best 7-1 mark. The only ACC team to be eliminated thus far has been Clemson.
The 11 teams from the Big East that began the tourney, meanwhile, have been reduced to just two after the event's first weekend.
The Big East has a 9-9 record in the tournament with only Marquette and Connecticut left to contend. Those two teams both defeated another Big East school to advance.
James made 6-of-8 shots from the field and grabbed 10 rebounds for Florida State (23-10). Michael Snaer added 13 points while both Derwin Kitchen and Okaro White had 10.
Notre Dame (27-7) was paced by Tim Abromaitis with 21 points.
Other than the three teams from the ACC and the two from the Big East, the tournament's Sweet 16 will include two clubs each from the Big Ten, Southeastern and Mountain West conferences along with one each from the Pac-10, Big 12, Atlantic 10, Colonial and Horizon.