The Week 4 AFC South matchup between the Tennessee Titans and the Houston Texans on September 28, 2025 carries a sense of urgency for both teams, as each enters the contest winless and desperate to avoid the dreaded 0–4 start that would all but derail postseason aspirations. Oddsmakers have given Houston the edge, opening the Texans as roughly 6.5-point favorites at home, a reflection of both the talent gap between quarterbacks and the struggles Tennessee has faced offensively through the first three weeks. The Texans’ hopes rest firmly on the shoulders of CJ Stroud, who has shown poise in his second season despite the team’s slow start, distributing the ball effectively and keeping Houston in games with flashes of explosive passing. Against a Titans defense that has struggled to cover deep routes and often buckles late, Stroud will have opportunities to push the ball vertically, provided the offensive line gives him enough protection against Tennessee’s inconsistent pass rush. Houston’s defense, meanwhile, has been opportunistic at times, but it will need to tighten up against the run and prevent Tennessee from controlling tempo with long, methodical drives, particularly after Titans head coach Brian Callahan made headlines by handing play-calling duties to quarterbacks coach Bo Hardegree in a bid to resuscitate his team’s stagnant offense.

For the Titans, this change could spark some life if the playbook opens up with quicker reads and more creative use of their backs and tight ends, but ultimately success will hinge on their ability to protect the quarterback and avoid negative plays that have defined their early season struggles. Both defenses are capable of creating turnovers, so whichever team wins the turnover battle will likely tilt the outcome in their favor. From a betting perspective, Houston’s 0–3 ATS record makes them a risky favorite, but Tennessee’s 1–2 ATS mark and inability to travel well has pushed public money heavily toward the Texans. The total sits around 44.5, a modest number that suggests oddsmakers expect a defensive struggle or at least a game where both offenses sputter at times; however, if Stroud finds rhythm early and the Titans respond to their offensive shakeup, the over could become viable. Ultimately, this matchup is about which team can steady itself under pressure and execute with discipline. The Texans have the quarterback edge, home-field advantage, and more public backing, while the Titans cling to the hope that changes in offensive leadership and a defensive stand can give them a chance to grind out a much-needed divisional win.