"It's nice to not pitch well and get a win," the right-hander said after Mike Lowell homered and Kevin Youkilis and Nick Green each drove in three runs to pace a 10-6 victory that stopped a four-game losing streak against the defending AL champions.
Wakefield (3-1) allowed five runs in five-plus innings to improve to 20-5 lifetime against the Rays, including a 10-3 record at Tropicana Field, where the Red Sox won for just the second time in their last 13 games in the domed stadium.
"The offense won the game," Wakefield said. "I was lucky enough to get through five, and the bullpen really picked me up."
Lowell hit a solo homer in the seventh off Brian Shouse. Youkilis had a two-run double off the left-hander in the sixth, while Green did most of his damage against Rays starter Jeff Niemann (2-3).
Carlos Pena hit his major league-leading 11th home run for Tampa Bay, a solo shot off Wakefield, who allowed seven hits, walked two and struck out five. The 20 wins against the Rays are his most against any team.
The Red Sox have won 13 of their last 16 games, but had sputtered in four consecutive losses to the Rays since Josh Beckett beat them at Fenway Park on opening day.
"We got on the board early," Boston manager Terry Francona said. "It's a lot easier to play that way than trying to come back."
Outscored 19-2 in the first two games of the series, the Red Sox pounced on Niemann for two runs in the first, three in the second and one in the third to build a 6-1 lead.
Green, who had three hits, got his first two RBI on a second-inning infield single that glanced off the glove of diving second baseman Akinori Iwamura. He drove in the final run off the Rays starter with a single in the third.
Niemann, who won the No. 5 starter's job in spring training, allowed six runs and seven hits in three innings, the shortest start of his career. The Rays nearly got him off the hook for the loss, scoring once in the fourth and three times in the fifth to trail 6-5.
Pena's homer was the first off Wakefield this season. Evan Longoria had a two-run double in the fifth, giving him 15 RBI against the Red Sox this year -- 10 in the first three games of this series.
Pat Burrell's RBI double trimmed Tampa Bay's deficit to one run before Boston pulled away for good.
"We had a chance to get back in, and back on top, but it just didn't work out," Rays manager Joe Maddon said. "I thought there was a lot of fight in us, but it's hard to fight back all the way every time."
The Red Sox loaded the bases against Grant Balfour in the sixth, and Youkilis sent his two-run double down the left field line for an 8-5 lead. Lowell led off the seventh with his fifth homer, and Youkilis drew a bases-loaded walk to drive in a second run in the inning.
Boston relievers Hideki Okajima and Ramon Ramirez worked three scoreless innings before Takashi Saito gave up a RBI single to Burrell in the ninth.
Red Sox LF Jason Bay left the game in the sixth with a left ankle bruise. He fouled a pitch off the ankle in the third inning. ... Boston DH David Oritz has gone 107 at-bats without a homer, his longest drought a 128 at-bat stretch from April 17-July 6, 2002. ... Longoria had four RBI in each of the first two games of the series. According to Elias Sports Bureau, he's the first player to drive in four or more runs against the Red Sox in conseuctive games since Manny Ramirez did it for Cleveland in September 2000. ... Injured Red Sox RHP John Smoltz, recovering from shoulder surgery performed last summer, could resume throwing Wednesday or Thursday. ... Rays pitching coach Jim Hickey was ejected during a pitching change in the seventh inning.