Wakefield, who had been stuck on 199 wins since July 24, had a shaky start on Tuesday but made the best of the Red Sox batters' offensive support to record the milestone.
"I'm very grateful," Wakefield told reporters.
"I'm very grateful that I've been able to wear this uniform as long as I have and reach the milestone I thought I'd never reach. Just very grateful."
Wakefield (7-6) allowed five runs, including two homers, over six innings against the Blue Jays, leaving the game with the Red Sox leading 6-5.
Boston pulled away with four runs in the sixth, then exploded for seven more in the eighth to snap a five-games losing streak and brighten their playoff outlook.
The Red Sox (86-61) now have a four-games lead over the Tampa Bay Rays (82-65) in the American League Wild Card race.
Dustin Pedroia finished the game 4-for-5 with two home runs and five RBIs to help make it a memorable night for his veteran pitcher.
(Writing by Jahmal Corner in Los Angeles; Editing by Peter Rutherford)