Ovechkin struck just 33 seconds into the game and added a second-period score as he surpassed the 40-goal mark for the seventh time.
Marcus Johansson and Joel Ward (empty net) added third-period goals for Washington, and Holtby picked up his seventh shutout and 30th win of the season.
James Reimer stopped 28 shots for Toronto, which has lost 16 straight road games.
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