Houston found the end zone twice in an 80-second span of the second quarter to open the scoring as Tennessee (6-4, 3-3 SEC East) capitalized on one of the game's six turnovers.
The Volunteers had 232 yards rushing -- nearly 80 more than their season average -- as they qualified for a bowl game for the 11th time in as many seasons under Coach Philip Fullmer.
Tennessee overcame the absence of starting quarterback Casey Clausen, who sat out the game after suffering an ankle injury in the second half of last week's 26-3 loss to Miami.
Tennessee, the 1998 national champion, has had a down year, losing four regular season games for the first time since 1994. It finishes the regular season against Vanderbilt and Kentucky.
Justin Griffith had a touchdown run for Mississippi State (3-7, 0-6 West), which remained the only winless team in the SEC West Division, dropping its third straight overall.
Houston opened the scoring with 9:18 left in the first half, finding the end zone from 34 yards out. Jerious Norwood fumbled on the Bulldogs' next play from scrimmage and Houston scored on a 10-yard run three plays later to make it 14-0.
Mississippi State cut it to 14-7 at halftime on a 10-yard touchdown pass from Kevin Fant to Donald Lee. But early in the third quarter, Mondre Dickerson sacked Fant and tackle Rashad Moore returned the fumble nine yards for a 21-7 lead.
The Bulldogs closed within 21-17 in the opening 90 seconds of the fourth quarter on a three-yard run by Griffith and 53-yard field goal by Brent Smith, but Tennessee put away the game with a pair of touchdowns 1:37 apart.
Jabari Davis capped an 80-yard drive with a one-yard run to increase the lead to 28-17. Elmore Wonsley fumbled the ensuing kickoff return and James Banks hit Jason Witten with a 29-yard touchdown pass on third and six to complete the scoring with 9:18 left.
Each team lost three fumbles.
Banks completed only three of eight passes for 90 yards, but the Volunteers scored more than 18 points for the first time in five games.
This was the first meeting between the teams since the 1998 SEC Championship. Tennessee leads the all-time series, 25-15-1.