For 2006, Huff was moved back to third base. He was placed on the disabled list for the first time in his career on April 12 with a sprained left knee suffered in a collision with Nick Green the day before. On May 4, he was activated from the DL. On May 19, he hit his first career walk-off home run against Yusmeiro Petit in a 10-inning, 5–4 win over the Marlins. Through July 9, Huff batted .283 with 65 hits, 15 doubles, 8 home runs, and 28 RBI in 63 games.