In Week 18, they secured the #2 seed in the NFC playoffs, then defeated the Philadelphia Eagles 31–15 in the Wild Card Round, notching postseason wins in consecutive seasons for the first time.

However, their title defense came to an end with a 30–27 last-second loss to the eventual Super Bowl champion Los Angeles Rams in the Divisional Round.

In addition, key weapons Rob Gronkowski, Ronald Jones, Leonard Fournette, Lavonte David, and Tristan Wirfs and others, all missed playing time dealing with various injuries.

As defending Super Bowl champions, the Buccaneers hosted the 2021 NFL Kickoff Game at Raymond James Stadium against the Dallas Cowboys.

With only one timeout left, trailing 29–28 with 1:24 remaining in regulation, Brady drove the Buccaneers 57 yards in eleven plays, down to the Cowboys 18-yard line.

On a rainy night, Brady was warmly welcomed by the Patriots fanbase, but quickly their attention turned to rookie quarterback Mac Jones.

In a back and forth game, turnovers, the lack of a rushing attack, and ultimately a missed field goal, cost New England a chance to win.

With Rob Gronkowski inactive due to a rib injury suffered the previous week, Tampa Bay struggled in the red zone.

Ryan Succop gave Tampa Bay an early 3–0 lead, but missed another field goal attempt to start the second quarter.

With Leonard Fournette and Ronald Jones the leading rushers on the night, Tampa Bay's more balanced offense again drove into the red zone, but had to again settle for a field goal.

Jakobi Meyers caught a 21-yard reception, then executed a flea flicker pass to Nelson Agholor, setting the Patriots up at the Tampa Bay 8-yard line.

Trailing 19–17, Mac Jones drove the Patriots into Tampa Bay territory, aided by a pass interference call on Jordan Whitehead.

The Colts crossed midfield, and Wentz threw a deep bomb to Michael Pittman Jr., but this time he was intercepted by Antoine Winfield Jr.

Isaiah Rodgers ran the ball back 72 yards to the Tampa Bay 32-yard line before Mike Edwards remarkably chased him down.

[29] After a quick incompletion, Carson Wentz's Hail Mary pass fell short of the endzone and was intercepted by Pierre Desir as time expired.

Four plays into the drive, Ryan's pass to Russell Gage was caught at the Tampa Bay 45, but punched out by Pierre Desir and the fumble was recovered by Carlton Davis.

Quarterback Tom Brady threw his 700th career touchdown pass (combined regular season & postseason), a game-winning, 58-yard catch and run to Breshad Perriman in overtime.

[34] Breshad Perriman was inactive on the COVID-19 list, while Antonio Brown and Mike Edwards were both serving the final game of a three-week suspension due to presenting counterfeit vaccination cards.

Brady and Zach Wilson (born 22 years apart to the day) set an NFL mark for the largest age gap between starting quarterbacks.

Tampa Bay received the second half kickoff, but an unsportsmanlike conduct penalty on Ryan Jensen, helped stall the drive.

Tampa Bay swept division rival Carolina, and secured the #2 seed in the NFC playoffs, winning their single-season franchise record 13th regular season game.

Minutes after Tampa Bay's game concluded, the Rams lost to the 49ers in overtime, effectively placing the Buccaneers in the #2 seed in the NFC playoff field.

The Eagles had to punt again, and Tampa Bay drove back for more points, this time moving the ball 53 yards in 11 plays to take a 17–0 lead with Ryan Succop's 34-yard field goal.

Brady started off the next drive with a screen pass to Bernard that picked up 21 yards, and eventually finished it with a 2-yard touchdown toss to tight end Rob Gronkowski, increasing the lead to 24–0.

Hurts then completed a pass to Smith for a two-point conversion to make the score 31–15, but any chance of a comeback was snuffed out when the Bucs recovered Philadelphia's onside kick attempt.

The Buccaneers' hopes of a second consecutive Super Bowl appearance came to an end at the hands of the fourth-seeded Los Angeles Rams, who upset the defending champions on a last-second 30-yard field goal by kicker Matt Gay.

Los Angeles built a 27–3 lead, but Tampa Bay rallied to score 24 unanswered points and tied the game with 42 seconds remaining in regulation.

Late in the second quarter, cornerback Nick Scott intercepted a pass by Tom Brady, setting up the Rams deep in Tampa Bay territory.

However, running back Cam Akers, making his first start of the season, was stripped of the ball at the Tampa Bay 1-yard line with 24 seconds left to leave the score 20–3 at halftime.

Seven plays later, facing a 4th & inches at the 9-yard line – with many expecting a quarterback sneak – Brady instead gave a handoff to Leonard Fournette who broke to the right untouched for a 9-yard touchdown.