López reached the playoffs as the Giants won the NL West for the first time since 2003. He made two appearances in the NLDS against the Atlanta Braves to face Jason Heyward, whom he struck out both times. The Giants won the series in four games. Against the Philadelphia Phillies in the NLCS, he made five appearances, all scoreless except for Game 4, in which he allowed a run. In the deciding Game 6, he pitched a scoreless seventh inning and was awarded with a win after Juan Uribe hit a game-winning home run against Ryan Madson in the eighth inning. López made two appearances against the Texas Rangers in the 2010 World Series, striking out the two batters he faced. In Game 2, he struck out Josh Hamilton to end the top of the eighth inning with a runner on second and preserve a 2–0 lead, although the Giants went on to win 9–0. He won his second World Series ring as the Giants defeated the Rangers in five games to win their first World Series since 1954.