Wakefield and the Sox, despite a couple of comeback attempts, suffered a 5-4 defeat to the Rays. That left Wakefield with a 9-1 record in his career at the Trop, and ended a six-game road trip for Boston in disappointing fashion.
After being swept in Toronto, the Red Sox took two out of three at Tampa Bay to finish the trip at 2-4.
Suffice it to say, this wasn't the day the Red Sox wanted the law of averages to catch up to their knuckleballer, who so loves to pitch with a roof over his head.
"We expect him, every time he takes the ball here, to win," said manager Terry Francona. "But I thought his ball had some life to it."
It took Wakefield 20 games -- 14 of which were starts -- to finally have an "L" next to his name in a game played at Tropicana Field.
"It's been a while," said Wakefield, who is 19-3 overall against Tampa Bay. "Couldn't have come at a worse time."
Wakefield was referring to the standings, as the Red Sox again saw their lead in the American League East reduced to 1 1/2 games by those torrid Yankees.
The Red Sox clinched their postseason footing on Saturday, but their goals did not end there.
"Everyone in this clubhouse wants to win the division," said Wakefield.
Only Wakefield remains from the last Red Sox team to win a division title, back in 1995. If the Red Sox are going to win this one, they'll need a successful six-game homestand against Oakland and Minnesota, which begins on Tuesday night at Fenway.
"Hopefully, we can get Manny [Ramirez] and [Kevin Youkilis] back," said utility infielder Alex Cora. "We want to win the division. We want to have the best record in baseball and start [the playoffs] at home."
As for Sunday's contest, the Rays struck first, getting a two-run homer from Delmon Young in the bottom of the second. Chances are that was the only pitch threatening to take away any sleep from Wakefield.
"Yeah, I felt fine today," said Wakefield, who has been stuck at 16 wins since Aug. 25. "I had good movement on my pitches, and I just made one mistake to Delmon Young. That was it."
While the Boston bats were basically silent early against Edwin Jackson, the Rays managed to chip away against Wakefield. Young again got things going in the fourth with a double to left. Jonny Gomes looped a single to left to make it 3-0. In the fifth, the Rays made it a four-run cushion on an RBI single to left by Jorge Velandia.
Doug Mirabelli, who made his return from a hamstring injury to catch Wakefield for the first time since Sept. 6, liked the view from behind the plate.
"His ball was moving all over the place," Mirabelli said. "I felt like he had an 'A' knuckleball today. He left one up to Young, and pretty much that was it."
Despite the four-run deficit, the Red Sox didn't quit. In fact, they stormed back in the sixth. With the bases loaded and nobody out, David Ortiz ripped a single off Jackson's leg. J.D. Drew got a one-out walk to force in a run. Coco Crisp's single up the middle brought home Cora, and the Sox were within one, at 4-3.
But even with the bases still loaded and just one out, the Red Sox couldn't do further damage. The rally ended when Jon Switzer induced Eric Hinske into a double play.
"We got our one big chance, and then Switzer got the double play which ends up ... anything is huge in a one-run game," said Francona.
Wakefield, in a rare mediocre outing at Tropicana Field, gave up seven hits and four runs over five innings. Then, just as the Red Sox were drawing close, the Rays got another run back in the bottom of the sixth, when Josh Wilson's bunt single scored Gomes. Cora got the Sox within one again on a solo homer in the top of the eighth.
Though the Red Sox had their share of late-inning comebacks this month against the Devil Rays, it was not to be on Sunday.
Instead, they packed their bags and eyed a strong finish in front of the Fenway faithful.
"I think we're always looking forward to getting home," said Francona. "It will be good for us. I'm not sure anybody really wants a day off right now. You play all year to get in games like this. I think our guys understand it."
Ian Browne is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.