In 2010, Uribe re-signed a one-year, $3.25 million contract with the Giants. He began 2010 as the Giants' second baseman because of an injury to Freddy Sanchez. At the beginning of May, he moved over to shortstop to replace the injured Rentería; for most of the remainder of the season, he was the Giants' starting shortstop. He hit a game-winning two-run home run on September 5 against Jonathan Broxton, turning a 4–3 deficit into a 5–4 victory over the Los Angeles Dodgers. On September 23, Uribe hit a grand slam against Ryan Dempster and a two-run home run in the second inning against the Cubs for a total of six RBIs, helping the Giants win 13–0.