Clowe got the puck after it glanced off another player's skate and knocked in the goal that turned out to be the game-winner with 6:39 to play.
Dan Boyle and Joe Pavelski also scored for the Sharks, who have won four of their last five games.
Phil Kessel and Tyler Bozak got the Leafs' goals.
San Jose's Evgeni Nabokov made 32 saves and Toronto's Jean-Sebastien Giguere had 23.
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