The Cardinals (28-8) will face California in the opener of the Final Four in New Orleans.
Jude Schimmel came off the bench to add 15 points and four rebounds. Bria Smith scored 13 and had nine boards.
Taber Spani led the second-seeded Lady Volunteers (27-8) with 20 points. Maighan Simmons and Kamiko Williams both scored a dozen.
Louisville broke from the gate quickly and led 41-26 at halftime. Tennessee got on track in the second half with 52 points, but could not catch the Cardinals, who shot 45.5 percent from the field and were a sizzling 18-for-21 from the free-throw line.