After a 34–3 win over the Miami Dolphins in Week 17, the Titans clinched the AFC South for the second consecutive season.

[6] Linebacker Davin Bellamy and defensive lineman Daylon Mack were signed to futures contacts the next day on January 14, 2021.

[8] Finally, defensive back Maurice Smith was signed to a futures contract on February 1, 2021.

Running backs (RB) Wide receivers (WR) Tight ends (TE) Defensive linemen (DL) Defensive backs (DB) Special teams Reserve Source:[17] The Titans' 2021 schedule was announced on May 12.

The Cardinals got up 17-0 in the second quarter before Tannehill ran in for a touchdown, however the extra point was missed by new kicker Michael Badgley.

However they came back to tie, with Derrick Henry scoring on a one-yard touchdown run with 29 seconds left, making it 30-30 and forcing the game into overtime.

The Titans defense also held the Colts to just 25% on third down conversions and sacked Carson Wentz two times with 10 quarterback hits.

Derrick Henry rushed 28 times for 113 yards, once again winning the FedEx Ground Player of the Week.

The Titans suffered several injuries in the game, with LB Bud Dupree already sidelined prior, WR A. J.

Brown exiting the game in the first quarter, WR Julio Jones being unable to play in the final stages, and losing CB Kristian Fulton for a stretch.

The game lead tied or changed five times as Ryan Tannehill, overcoming seven sacks, completed a two-yard score to Cameron Batson that forced overtime.

With the win the Titans moved to a 9-2 lifetime record against Chiefs coach Andy Reid.

But running back Derrick Henry was lost for the rest of the regular season with a foot injury that necessitated surgery and also the signing of Adrian Peterson.

In their first game without Henry, the Titans accounted for just 194 total yards on offense, but won due to a strong performance by their defense, which set up several short fields and intercepted Rams quarterback Matthew Stafford on two consecutive plays in the second quarter, with the second pick being returned for a touchdown.