Running backs (RB) Wide receivers (WR) Tight ends (TE) Defensive linemen (DL) Defensive backs (DB) Special teams Reserve Source:[9] The Titans' preseason opponents and schedule were announced in the spring.

On May 9, the NFL announced that the Titans would play at the Buffalo Bills at 6:15 p.m. CDT on September 19, as part of ESPN's Week 2 Monday Night doubleheader.

The Titans blew a 13–0 lead and lost to the Giants, 21–20, on a one-yard pass from Daniel Jones to Saquon Barkley.

The Titans flew to Orchard Park for their matchup against the Bills as part of a Monday Night Football doubleheader.

The Bills took the opening kickoff and stormed down the field with a methodical 12-play touchdown drive to grab an early 7–0 lead.

Josh Allen then hit Stefon Diggs for the first of three touchdowns on the night for him; a sack by the Bills' defense capped off the first half, with Buffalo holding a 17–7 lead.

In the third quarter, the Bills blew the game open after Allen hit Diggs for the second of three touchdowns for the pair on the night; the Titans were quickly forced into a punt which Bass converted into his second field goal.

The offense capitalized on the turnover and exploited the already-exhausted Titan defense for Diggs's third touchdown catch of the night.

They lost their fifth straight, dropped below .500 for the first time since Week 3, and fell out of first place in the AFC South lead, as they lose the head-to-head tiebreaker to Jacksonville.