Going into 2007, Anthony Castrovince of MLB.com reported that Garko would have to improve on the defensive end to make the 25-man roster because the Indians already had a first baseman in Casey Blake. Towards the end of spring training, Indians' manager Eric Wedge noted that Garko had made improvements on defense. He made the 2007 roster out of spring training for the first time in his career. On April 22, Garko hit a game-winning three-run home run in the top of the ninth inning against the Tampa Bay Rays. He became the everyday starting first baseman early in the season after Casey Blake moved to third base because of an injury to Andy Marte. He began to dislike interleague play because during it, designated hitter Travis Hafner was moved to first base, which forced Garko to the bench. On July 18, Garko hit a two-run home run in the ninth inning against Chicago White Sox' pitcher Bobby Jenks to tie the score at five-to-five, and then drove in an RBI run for the win in the eleventh inning. During the regular season, Garko batted .289 with 29 doubles, one triple, 21 home runs and 61 RBIs in 138 games. He was third in the league with 20 hit by pitches (an Indians single-season record). In the postseason, he hit .314 with two doubles, one home run, and five RBIs in nine games. The Indians defeated the New York Yankees in four games in the American League Division Series before losing the American League Championship Series in seven games to the Boston Red Sox.