After starting the year with just three wins from six games, Tom Brady's men would have looked upon the Panthers fixture as a catalyst to get their season back on track.
The Panthers had other ideas, however, with a dominant rushing game contributing to the team's three touchdowns.
The Buccaneers, meanwhile, struggled mightily on both sides of the ball - a late field goal the sole bright spot on an otherwise dark day.
It was also a tough outing for Brady's veteran rival Aaron Rodgers, as the Green Bay Packers were pipped by the Washington Commanders 23-21.
Despite a late Green Bay touchdown keeping things close, a 10-point third quarter ultimately proved enough for the Commanders to claim their third win of the year.
Rodgers threw for 194 yards and two touchdowns as the Packers suffered their third-straight defeat.
The New York Giants continued their rise by dispatching the Jacksonville Jaguars to extend their winning streak to four.
Daniel Jones threw for one touchdown and ran in for another en route to a 23-17 victory.
Patrick Mahomes and the Kansas City Chiefs turned around a dismal first quarter to sail home with four second-half touchdowns to beat the San Francisco 49ers 44-23.
The Cleveland Browns were left to rue a series of costly errors as they were unable to chase down the Baltimore Ravens in a 23-20 loss.
Tua Tagovailoa had a successful return from injury as he led the Miami Dolphins to a 16-10 win over the Pittsburgh Steelers.
The New York Jets remain undefeated on the road after eclipsing the Denver Broncos 16-9.
Elsewhere, there were big wins for the Tennessee Titans, Cincinnati Bengals, Dallas Cowboys, Las Vegas Raiders and Seattle Seahawks.