Bruce Massey scored 17 points to lead the Blue Raiders (9-3), who ended the game on a 16-3 run to get their first win against Vanderbilt since 1995.
After Knight's layup, Kerry Hammonds plucked a steal from Kedren Johnson and finished with a layup for a three-point cushion. Johnson missed a 3-pointer and Raymond Cintron's free throws with 7.5 seconds left sealed the win.
The Commodores (5-5) led 49-40 with 9:58 left but went scoreless for nearly the next six minutes.
Johnson scored 15 of his 25 points in the first half to lead Vanderbilt. He banked in his final basket with 1:56 left to give Vanderbilt a 52-51 lead before Knight responded.
Hammonds scored a season-high 11 points for Middle Tennessee, which had lost five straight against its in-state neighbors from 38 miles away.
The game had five ties and 10 lead changes. Vanderbilt, which had won three in a row, appeared in control early in the second half.
Johnson scored four straight points to end a 10-2 run as the Commodores feasted on 20 turnovers by Middle Tennessee. Johnson's jumper with less than 10 minutes to go catapulted Vanderbilt to its largest lead.
The Blue Raiders slowly charged back. After consecutive baskets by Massey, Shawn Jones and Knight each scored off offensive rebounds to cut the lead to 49-48 with 4:36 left.
A minute later, Cintron drove the lane to give the Blue Raiders their first lead since late in the first half. Johnson answered with a tough shot inside.
Knight missed his first layup but wrestled for the rebound with Vanderbilt center Josh Henderson to force a jump ball in favor of Middle Tennessee. The Blue Raiders pounced on the second-chance opportunity. Marcos Knight lofted a pass to his younger brother, who came open for an easy layup.
Middle Tennessee grabbed 14 offensive rebounds for 12 second-chance points and won the rebounding battle 34-25.
The Commodores had won 29 of 33 in the all-time series. The game was played downtown at Bridgestone Arena, marking the first neutral-site contest between the schools.
In a foul-riddled first half, the Blue Raiders grabbed their largest lead when Marcos Knight finished a 3-point play for a 12-5 lead five minutes in.
Middle Tennessee went quiet from there, failing to score for the next seven minutes.
Vanderbilt charged ahead for a five-point lead and used the foul line to its advantage. The Commodores made 10 of 13 in the first half and the teams combined for 23 free throws.
When Marcos Knight was called for his second foul and the 10th team foul with 8:56 left in the half, Middle Tennessee coach Kermit Davis didn't agree. The officials disagreed with Davis, who was whistled for a technical foul. Kyle Fuller missed both foul shots for the technical but Johnson sank his two free throws to give Vanderbilt a 17-12 lead.
The technical woke up the Blue Raiders — Hammonds and Knight in particular. The duo combined for the team's final 17 points of the half. Hammonds hit a go-ahead 3-pointer. After Vanderbilt regained the lead, Massey banked in a shot with 42 seconds left for a 31-31 tie at halftime.
Vanderbilt stunned by MTSU, 56-52
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