Henderson is the Southeastern Conference's leading scorer with 18.9 points per game and he put on a show after the break, nearly single-handedly carrying the Rebels (16-2, 5-0 SEC) to their eighth consecutive victory. He scored 32 against the Volunteers just two weeks ago in a win in Knoxville.
It's only the second time Ole Miss has started 5-0 in SEC play.
Reginald Buckner added 10 points in a foul-filled game that made both teams go deep into the bench.
Tennessee (9-8, 1-4) led for much of the game, but couldn't withstand Henderson's hot shooting. Jordan McRae led the Volunteers with 26 points while Trae Golden added 11.
The shots weren't falling for either team early, and a constant stream of fouls didn't help the rhythm.
By midway through the first half, the starting big men for both teams were relegated to the bench because of foul trouble.
Tennessee made a few more shots than the Rebels to take a 25-18 lead into halftime. It was the fewest points by an Ole Miss team in the first half since 2009.
Golden led all scorers with seven points.
One reason Ole Miss couldn't find the basket was the Volunteers' lockdown defense on Henderson in the first half. He was matched step for step by a host of Tennessee defenders early and scored just four points in the first half — all on free throws.
The 6-foot-2 junior got going early in the second half, hitting two 3-pointers to finally spark the Rebels' offense. Nick Williams made another 3-pointer to give Ole Miss a 33-32 lead with 14:15 remaining.
But the Rebels couldn't stop fouling McRae and the 6-5 junior just kept sinking free throws. He hit eight free throws in a row midway through the second half to help the Vols pull ahead 46-40 with 8:51 left.
That's when Henderson picked up the Rebels and carried them by himself, hitting shot after shot. He finished 7 of 16 from the field, including 6 of 15 from 3-point range (40 percent).
After shooting just 4 of 23 in the first half (17.4 percent), the Rebels bounced back with a 14 of 26 (53.8 percent) performance in the second half.
Tennessee had 21 turnovers and missed four crucial free throws in the final few minutes. The Volunteers outrebounded the Rebels 41-30.
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Read more in Friday's NEMS Daily Journal newspaper.