Clemson was looking for its second straight road win Wednesday night after edging N.C. State in Raleigh last Saturday, but Notre Dame would have none of it.
The Irish (10-5, 4-1) controlled the Tigers (10-6, 2-3) all night en route to a 72-56 win.
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P.J. Hall led the Tigers in scoring (14) and rebounds (7) while Notre Dame's Dane Goodwin turned in a game-high 21 points.
Clemson got on the board on its first possession following a Hall layup. The Tigers' brief 2-0 advantage would be their only lead of the night.
Notre Dame quickly surged to a 17-6 lead within the first five minutes of play after a Goodwin layup.
Hunter Tyson's three-pointer with just under 12 minutes remaining before halftime would pull Clemson to within five at 19-14, but the Tigers would come no closer for the remainder of the game.
From there, the Irish went on an 8-0 run to open up a 27-14 advantage, capped by a Cormac Ryan three-pointer. Notre Dame would go on to claim a 39-22 lead at intermission.
The Irish led by as much as 23 in the second half, but with just over 13 minutes remaining the Tigers began to cut into the deficit on a brief 10-3 run.
An Alex Hemenway free throw would pull Clemson to within 14 with just over one minute left in regulation before another Ryan three-point basket put a bow on Notre Dame's 16-point victory.
Notre Dame shot 45.5-percent from the floor and hit 10-of-26 three-point attempts (38.5%) while the Tigers shot just 34.4% and converted a mere six of 32 shots from long range (18.8%).
Blake Wesley joined Goodwin as one of two Irish players in double figures, scoring 20 points.
Tyson added 12 points for the Tigers on 4-of-8 shooting, while Nick Honor was 0-for-6 from the floor. Al-Amir Dawes added just six points on 2-of-11 shooting.
Clemson head coach Brad Brownell fell to 2-7 all-time versus Notre Dame.
The Irish will travel to Blacksburg to face Virginia Tech on Saturday.
Clemson will return home to host Boston College on Saturday. The game is set for a 6:30 p.m. tip.
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