On July 2, 2006, Uribe had five RBIs in a 15–11 loss to the Chicago Cubs; two days later, he again had five RBIs in a 13–0 victory over the Baltimore Orioles. Uribe had one of his best power seasons in 2006, batting .235 with 21 home runs and 71 RBIs in 132 games. However, he had the lowest on-base percentage of his career, at .257. Injuries prevented him from appearing 10 games, and he also lost some starts at shortstop to Alex Cintrón because of his low on-base percentage. He led the White Sox in sacrifice hits and ranked fourth in the AL with a .977 fielding percentage. He also joined Derek Jeter, Miguel Tejada, Édgar Rentería, and Michael Young as the only shortstops to top 70 RBIs in 2004, 2005, and 2006.