He hit .288 with 12 home runs in 82 games. Although he usually only started against left-handed pitchers, Thames came through with several big hits in 2010. On May 17, he hit a walk-off home run against Red Sox closer Jonathan Papelbon. On July 4, Thames returned from a DL stint to hit a game-ending single against the Toronto Blue Jays. On August 11, he helped the Yankees come back from a five-run deficit by hitting a home run in the eighth inning and a go-ahead single in the ninth inning to beat the Rangers. In a six-game stretch from August 24 to 30, he had 6 home runs and 11 RBIs in 21 at-bats.