Henry surpassed the milestone in the fourth quarter and finished with 250 rushing yards and two touchdowns on 34 carries in the Titans' last-second victory. The win gave Tennessee the AFC South title.
The 26-year-old Henry becomes only the eighth player in NFL history to record at least 2,000 rushing yards in a single season, joining O.J. Simpson, Eric Dickerson, Barry Sanders, Terrell Davis, Jamal Lewis, Chris Johnson and Adrian Peterson. The Titans are the only team to have two players -- Henry and Johnson -- rush for more than 2,000 yards in a season.
Before Henry, Peterson was the last running back to achieve the feat when he racked up 2,097 yards in 2012.
Henry had more than 200 rushing yards for the third straight game against the Texans, making him the only player in league history to do so. The former Alabama star also joined former New York Giants tailback Tiki Barber (2005-06) as the only players to end with 200-yard games in back-to-back season finales.
Henry will finish the 2020-21 regular season as the league leader in rushing yards, touchdowns and attempts.
The Titans (11-5) will face the Baltimore Ravens (11-5) in the wild-card round next weekend.