Middlebrooks became the first Red Sox player to sock three homers in a game since Dustin Pedroia pulled off the feat June 24th, 2010.
Jon Lester (2-0) earned the victory, allowing five hits over seven scoreless innings. He struck out six and didn't issue a walk in the victory.
Toronto's R.A. Dickey (0-2) was roughed up in his second consecutive start to begin the season, yielding eight runs -- seven earned -- on 10 hits over 4 2/3 innings.
The newly signed knuckleballer fell 4-1 in his debut against Cleveland Tuesday.