HOUSTON — Ryan Fitzpatrick passed for 358 yards and a career-best six touchdowns in his return to the starting lineup to lead the Houston Texans to a 45-21 victory over the Tennessee Titans on Sunday at NRG Stadium.

Fitzpatrick, benched following a loss to the Philadelphia Eagles earlier this month, completed 24 of 33 attempts and posted a 147.5 passer rating substituting for Ryan Mallett, who was lost to a season-ending pectoral injury. Fitzpatrick tossed a pair of scoring passes to wide receiver DeAndre Hopkins, whose 238 receiving yards represented a career best.

Texans defensive end J.J. Watt also got in on the act, catching a 1-yard touchdown pass from Fitzpatrick after his sack of quarterback Jake Locker resulted in a fumble. Watt recovered the fumble and his short return delivered Houston (6-6) possession at the Titans 24-yard line.

Watt has accounted for five touchdowns this season, three on offense.

Tennessee (2-10) dropped its sixth consecutive game. After surrendering 212 rushing yards to the Texans in the first meeting between the AFC South rivals on Oct. 26, the Titans allowed just 99 rushing yards on Sunday. But their inability to mount a pass rush against Fitzpatrick enabled him to pick apart the Titans secondary.

The Texans secured a 14-0 lead with haste, covering 80 yards on 14 plays on an opening drive capped by an 8-yard Fitzpatrick touchdown pass to tight end Ryan Griffin. Texans cornerback Johnathan Joseph followed with an interception of Titans quarterback Zach Mettenberger, a turnover that returned possession to the Texans at the Tennessee 20.

Four plays later, Fitzpatrick hit running back Arian Foster for a 7-yard scoring toss. Just prior to the intermission, Fitzpatrick and Hopkins completed the first of their two scoring connections, with Hopkins hauling in a 58-yard strike with 38 seconds left for a 24-0 lead.

Mettenberger passed for 184 yards and a score before leaving with an injury. Watt levied the blow that knocked Mettenberger from the game.

NOTES: The Texans’ 24-point halftime lead was their largest at the intermission this season. … With his 36-yard scoring grab in the third quarter, Titans WR Kendall Wright set a personal single-season mark with five touchdown receptions. That catch was his 50th on the season, making Wright the second player in franchise history (Ernest Givins, 1986-88) with 50 receptions in each of his first three seasons. … Texans QB Ryan Fitzpatrick became the eighth quarterback in league history to throw four touchdown passes in a game for three franchises (Buffalo, Tennessee). … Titans QB Zach Mettenberger was lost to a right shoulder injury midway through the third quarter and did not return.