Tennessee (20-5, 11-1 Southeastern Conference) hasn't failed to win at least 20 games since going 16-11 in 1975-76. This latest victory gave Tennessee a half-game lead in the SEC standings over No. 11 Texas A&M (20-5, 10-1), which hosts No. 9 Kentucky (22-3, 10-2) on Monday.
Vanderbilt has never beaten Tennessee at Knoxville in 28 attempts. Tennessee leads the all-time series with Vanderbilt 62-8.
Ariel Massengale scored 14 points, Bashaara Graves had 13 points and Jasmine Jones and Taber Spani each added 12 points for Tennessee.
Jasmine Lister matched a career high with 24 points for Vanderbilt (16-9, 6-6), while Morgan Batey and Heather Bowe each added 10 points.
Tennessee pulled away by going on a 16-4 spurt midway through the game. The Lady Vols were clinging to a 33-29 lead before scoring the last six points of the first half. They opened the second half with a 10-4 run and led by double digits the rest of the way.
Vanderbilt is playing without three players projected as starters in the preseason.
The Commodores played a second straight game without 2011-12 SEC scoring leader Christina Foggie, who injured her right knee last weekend against Kentucky. Vanderbilt guard Kady Schrann missed her third consecutive game with an ankle injury. Vanderbilt has played the entire season without center Stephanie Holzer, who dislocated a knee in a preseason exhibition.
Vanderbilt got more bad news Sunday when starting forward Tiffany Clarke got sick at halftime and didn't play in the second half after scoring seven points and pulling down five rebounds in the first 20 minutes.
That lack of depth eventually wore Vanderbilt down, though the Commodores made Tennessee work for the victory.
For most of the first half, Tennessee would build a lead, only to watch Vanderbilt close the gap.
Tennessee made six of its first eight shots to grab an early 14-5 advantage, but Vanderbilt tied the game by going on an 11-2 run. After Tennessee went on a 9-2 spurt to take a 25-18 lead, Vanderbilt cut the margin to two. Tennessee got the lead up to nine again at 33-24, but Vanderbilt got back within four before the Lady Vols took control for good.
Tennessee led by as many as 20 points in the second half. Vanderbilt scored 10 straight points to cut the lead to 10 with 8:40 remaining, but the Commodores couldn't get the margin into single digits.
Both teams wore different shades of pink uniforms in honor of Tennessee's annual "Live Pink, Bleed Orange" game to raise breast cancer awareness and support the Kay Yow Cancer Fund.
Before the game, the Champions For A Cause foundation founded by Tennessee coach Holly Warlick and LSU coach Nikki Caldwell presented separate $15,000 checks to three organizations: The Kay Yow Cancer Fund, the UT Breast Health Outreach Program and the Brady James Foundation.
Warlick's older sister, Marion Ferrill, underwent a double mastectomy last fall, but her cancer now is in remission. Ferrill has been at all the Lady Vols' home games this season and was in the stands Sunday as well.
Breast cancer survivor and "Good Morning America" host Robin Roberts attended the game and sat next to former Lady Vols coach Pat Summitt. Roberts left "Good Morning America" last year to undergo a bone marrow transplant to treat a rare blood disorder, but she is scheduled to return to the show Wednesday.