Kevin Youkilis tripled, homered and scored three runs for Boston.
Wakefield's knuckleball, which was clocked in the mid 60s, clearly confused the Phillies. He allowed five hits and two walks in earning his first win since July 8, 2009, against Oakland. Wakefield (1-2) also earned his 190th career victory as the Red Sox took two of three from the Phillies.
"I had a pretty good feel with everything and our offense did a good job," Wakefield said.
The win for Wakefield was his first in 13 appearances -- nine starts -- since his last victory.
Getting an early lead against a hot-hitting team boosted his confidence.
"It helped a lot," Wakefield said. "I was able to throw my pitches and get outs. I didn't have to worry about walks."
Youkilis had a triple to open the second and a towering homer to left in the sixth off Halladay, giving the Red Sox a 4-0 lead. Youkilis is 21 for 58 in his career against Halladay.
"He's a good hitter who doesn't give at-bats away," Red Sox manager Terry Francona. "He's been terrific."
Halladay (6-3) was hit hard a start after he didn't appear to have his best stuff in a 132-pitch complete game effort against Pittsburgh on Tuesday, a 2-1 loss. On Sunday, Halladay, who has a major league-leading four complete games, saw his ERA jump from 1.64 to 2.22 after allowing eight hits and seven runs six earned in 5 2/3 innings.
"I felt good," Halladay said. "A of couple things didn't go the way I wanted to early."
Halladay got what appeared to be a perfect inning-ending double play ball in the fourth, but Adrian Beltre's soft grounder went straight through third baseman Greg Dobbs' legs, allowing two runs to score for a 3-0 advantage.
"His game was better than what it indicated," Philadelphia manager Charlie Manuel. "I felt like his stuff was good. He can pitch better. At the same time, his stuff was good."
Youkilis led off the second with a triple to deep center field, which bounced out of Shane Victorino's glove as he jumped for the ball. J.D. Drew followed with an RBI grounder to first, scoring Youkilis for a 1-0 lead.
- The sellout was the 65th in a row at Citizens Bank Park. The Phillies became the first team in the majors to surpass one million in attendance this season.
- Red Sox OF Mike Cameron, who has been on the disabled list since April 20 with a lower abdominal strain, played in a rehab assignment with Double-A Portland on Sunday. He doubled in his first at-bat.
- Drew was in the starting lineup despite a nagging hip flexor.
- Wakefield was on the verge of registering his first shutout since July 29, 1997, against Seattle a 4-0 win over Randy Johnson.
- Gload's pinch-hit homer was his second of the season and seventh of his career.