Wakefield allowed just four hits and one run over seven strong innings.
"He can't be as good as he was last time we faced him -- he was lights-out," Jays second baseman Aaron Hill said.
The series against Toronto marks the end of a stretch that has Boston playing 10 of 13 at Fenway Park.
The Sox are in the second stop of a three-city, seven-game road swing against AL East opponents to face the Jays, who are two games under .500 for the first time this season.
"It's just April and you're playing in your division, and I think that's how most teams break in [the season]," said Red Sox right fielder J.D. Drew. "You just want to accumulate wins and do it early if you can."
Toronto went 6-3 at Fenway Park last year.
BOS: RHP Tim Wakefield (2-1, 1.35 ERA)
Wakefield's knuckleball has been in top form in his first three starts; he's allowed one earned run each time out. Lifetime against the Jays, Wakefield is 13-8.
TOR: RHP Tomo Ohka (0-2, 7.02 ERA)
Ohka turned in his best start of the young season last time out, limiting the Red Sox to four runs on four hits in 6 1/3 innings. The right-hander carried a no-hitter into the fifth inning before yielding the first of three solo home runs in defeat. That trip to the mound was Ohka's only career appearance against Boston, but he pitched for the Red Sox for parts of the 1999-2001 seasons. Ohka is 3-8 with a 3.95 ERA in 17 career games at Fenway Park.
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Jonathan Papelbon has converted all six save chances this season and is a perfect 16-for-16 in his career during April after closing out the Yankees on Sunday night.
Official game notes
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Tuesday: Red Sox (RHP Julian Tavarez, 0-1, 6.75) vs. Blue Jays (RHP Roy Halladay, 2-0, 2.37), 7:05 p.m. ET
Wednesday: Red Sox (RHP Curt Schilling, 2-1, 3.81) at Orioles (RHP Daniel Cabrera, 1-1, 4.10), 7:05 p.m. ET
Thursday: Red Sox (RHP Josh Beckett, 4-0, 2.55) at Orioles (LHP Adam Loewen, 2-0, 3.72), 7:05 p.m. ET