WEEK 1 vs. ARIZONA: The Titans open the season at home for the first time since 2017, leading off against the Arizona Cardinals (Sept. 12) for the first time in franchise history. Arizona makes its third regular season appearance at Nissan Stadium and its first since 2013. In 2020, Cardinals quarterback Kyler Murray passed for 3,971 yards and 26 touchdowns and rushed for an additional 11 touchdowns after winning 2019 NFL Rookie of the Year honors.
WEEK 2 at SEATTLE: The Titans embark on their third all-time trip to CenturyLink Field to meet the Seattle Seahawks on Sept. 19. They split the two previous meetings in 2009 (Titans win) and 2013 (Seahawks win).
WEEKS 3 & 8 vs. INDIANAPOLIS: The Titans host their first divisional game of 2021 on Sept. 26 and could get their first look at veteran quarterback Carson Wentz since he was traded from Philadelphia and reunited with Colts head coach and former Eagles offensive coordinator Frank Reich. The Titans enter 2021 with a three-game winning streak within the AFC South after taking all three road matchups with divisional foes in 2020.
WEEK 4 at NEW YORK JETS: On Oct. 3, the Titans play the Jets at MetLife Stadium for only the second time. The Jets are launching a new era in 2021 with rookie quarterback Zach Wilson and first-year head coach Robert Saleh, and they also signed former Titans wide receiver Corey Davis as an unrestricted free agent this offseason.
WEEKS 5 & 14 vs. JACKSONVILLE: The Titans enter 2021 with a three-game winning streak over the Jaguars and have won seven of their last eight games in the series.
WEEK 6 vs. BUFFALO: The Bills visit Nissan Stadium (Oct. 18) for the third consecutive season and for the second consecutive year in primetime. The Titans defeated the Bills on a Tuesday night in 2020, following a two-day postponement due to a COVID-19 outbreak. In 2020, Titans quarterback Ryan Tannehill and Buffalo's Josh Allen became the fourth and fifth quarterbacks in NFL history with at least 3,800 passing yards, 33 passing touchdowns and seven rushing touchdowns in the same season. The Titans have won seven of their past nine Monday night games, including most recently their 2020 season opener at Denver.
WEEK 7 vs. KANSAS CITY: On Oct. 24, the Titans and Chiefs tangle for the first time since the 2019 AFC Championship game. Prior to Kansas City's conference-clinching victory, the Titans had won their previous four games versus the Chiefs, including three wins in Kansas City. Chiefs quarterback Patrick Mahomes, the 2018 NFL MVP, passed for 4,740 yards, 38 touchdowns and six interceptions in 2020.
WEEK 9 at LOS ANGELES RAMS: On Nov. 7, the Titans make their first appearance at SoFi Stadium, clashing with the Los Angeles Rams and their new veteran quarterback Matthew Stafford on Sunday Night Football. The last time the Titans franchise played a game in Los Angeles was Oct. 30, 1994 against the then-Los Angeles Raiders.
WEEK 10 vs. NEW ORLEANS: New Orleans travels to Nashville for only the fourth time in the regular season (Nov. 14) but for the second time in three years. The Saints most recently visited in 2019 and were added to the Titans' 2021 home slate with the advent of the NFL's 17-game schedule.
WEEKS 11 & 18 vs. HOUSTON: Titans running back Derrick Henry enters the Nov. 21 game at Nissan Stadium carrying a three-game streak with more than 200 rushing yards against the Texans. On Jan. 9, the Titans will appear in their first Week 18 contest, closing out the campaign at Houston for the third consecutive season.
WEEK 12 at NEW ENGLAND: The Titans visit New England (Nov. 28) for the first time since a 2019 playoff victory at Gillette Stadium. General manager Jon Robinson and head coach Mike Vrabel return to where they spent significant portions of their scouting and playing careers, respectively.
WEEK 13 (BYE): The Week 13 bye is tied for the latest Titans bye in franchise history, matching the week of their off date in 2016.
WEEK 15 at PITTSBURGH: At Pittsburgh on Dec. 19, new Titans outside linebacker Bud Dupree could play his former team for the first time since headlining the Titans' 2021 unrestricted free agent signings. It will mark the 80th all-time game (regular season and postseason) between the organizations in a rivalry that dates back to 1970. No other opponent has faced the Titans/Oilers franchise as many times as the Steelers.
WEEK 16 vs. SAN FRANCISCO: In a nationally-televised game on Thursday Night Football, San Francisco makes its third regular season appearance at Nissan Stadium (Dec. 23). San Francisco quarterback Trey Lance was the third-overall selection in the 2021 NFL Draft and is the former North Dakota State teammate of Titans second-round rookie tackle Dillon Radunz. It will mark the first Thursday night game for the Titans franchise against an NFC opponent (excluding Thanksgiving daytime kickoffs).
WEEK 17 vs. MIAMI: The Dolphins visit Nissan Stadium (Jan. 2) for the first time since 2015. The last three meetings between the teams have taken place at Hard Rock Stadium. Titans quarterback Ryan Tannehill has not played his former team since being traded from the Dolphins to the Titans in 2019. The Dolphins made him the eighth-overall selection in the 2012 NFL Draft.