Junior guard Gabby Williams and sophomore guard Katie Lou Samuelson each finished with 23 points for the Huskies, who won their 109th consecutive game overall -- including 26 straight in the NCAA Tournament.
The Huskies (34-0) advance to face the winner of Texas AM-UCLA on Saturday in the Sweet 16 in Bridgeport, Conn.
It is the 24th straight trip to the Sweet 16 for UConn, and Huskies coach Geno Auriemma moved within one of the late Tennessee coach Pat Summitt in all-time wins in the NCAA Tournament.
Nurse, who tied the NCAA Tournament record with the nine 3-pointers, scored 26 points in the first half while Syracuse had 29 points at intermission.
Senior guard Alexis Peterson scored 25 points, and senior guard Brittney Sykes finished with 15 for the Orange.
UConn beat Syracuse 82-51 in last year's national championship game. Monday's rematch was equally as lopsided.
Connecticut stormed out to a 28-11 lead after the first quarter. With Nurse leading the charge, the advantage ballooned to 57-29 by halftime. Nurse hit eight 3-pointers in the first half, and the Huskies had 21 field goals on 20 assists.
Syracuse (22-11) never seriously challenged the Huskies, who are shooting for their fifth straight national championship.
Freshman guard Gabby Cooper, who hit a school-record eight 3-pointers in the Orange's first-round win over Iowa State, was held to nine points.
Connecticut sophomore guard Napheesa Collier finished with 17 points and seven rebounds.
The Huskies shot 62.3 percent from the field and outscored Syracuse 16-4 at the free-throw line.
UConn finished with 30 assists on 33 field goals.