In 2005, Huff spent most of the year in right field. On April 18, Huff had four RBI and hit the 100th home run of his career, a three-run shot against Jaret Wright in a 19–8 loss to the Yankees. After hitting 5 home runs in the first three months, Huff hit 17 home runs through the rest of the season. On July 22, he hit the first grand slam of his career, a game-winning home run against Bruce Chen in a 7–5 victory over the Orioles. He was named the AL Player of the Week from July 25 to 31 after he batted .409 with two home runs and 10 RBI. In 148 games, Huff batted .261 with 150 hits, 26 doubles, 22 home runs, and 92 RBI.