^ abThe Titans traded WR A. J. Brown to the Philadelphia Eagles in exchange for first- and third-round selections (18th and 101st overall).[1]
^ abcdeThe Titans traded first- and third-round selections (26th and 101st overall) to the New York Jets in exchange for second-, third- and fifth-round selections (35th, 69th and 163rd overall).[1]
^The Titans traded a second-round selection and a 2023 fourth-round selection to the Atlanta Falcons in exchange for WR Julio Jones and a 2023 sixth-round selection.[2]
^ abcThe Titans traded third- and fifth-round selections (90th and 169th overall) to the Las Vegas Raiders in exchange for a third-round selection (86th overall).[1]
^ abThe Titans' were awarded compensatory picks in the 4th and 6th rounds due to losses in free agency.[3]
^The Titans traded OL Isaiah Wilson and a seventh-round selection (247th overall) to the Miami Dolphins in exchange for a 2021 seventh-round selection.[4]
On May 9, the NFL announced that the Titans will play at the Buffalo Bills at 6:15 p.m. CDT on September 19, as part of ESPN's Week 2 Monday Night doubleheader.[7]
The remainder of the Titans' 2022 schedule, with exact dates and times, was announced on May 12.
The Titans stormed down the field and scored on their first drive, then added two field goals in the second quarter to grab a 13–0 at halftime, but big plays by Daniel Jones and Saquon Barkley in the second half led to the Giants capturing a 21–20 lead. Ryan Tannehill and the Titans' offense mounted an impressive last-second drive to get into field goal range, but Randy Bullock missed the game-winning attempt as time expired. With the shocking loss, the Titans fell to 0–1.
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. The Titans responded with a 9-play drive capped off by star running back Derrick Henry's 2-yard touchdown run. From that point on however, it was all Bills. It started when kicker Tyler Bass converted a 49-yard field goal to go up by 3. 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. Following the score, Tannehill was picked off at the Bills' 49-yard line. The offense capitalized on the turnover, and exploited the already-exhausted Titan defense for Diggs's third touchdown catch of the night. On the Titans' next drive, Tannehill was again picked off, the interception this time going all the way back for six courtesy of Matt Milano. By this point, the Bills had scored 24 points in the third quarter to grab a commanding 41–7 lead. Both teams' defenses took over for the rest of the game, but by this point the game had long been decided.
^ abTennessee wins tie break over Kansas City based on conference record.
^ abNY Jets wins tie break over Miami based on head-to-head victory.
^ abNew England wins tie break over Cincinnati based on conference record.
^ abCleveland wins tie break over Denver based on strength of victory.
^ abJacksonville wins tie break over Pittsburgh based on conference record.
^When breaking ties for three or more teams under the NFL's rules, they are first broken within divisions, then comparing only the highest ranked remaining team from each division.
Legend
w — Clinched wild card
x — Clinched playoff berth
y — Clinched division
z — Clinched first-round bye and home-field advantage