Cain reached the playoffs for the first time in his career as the Giants won the NL West to reach the playoffs for the first time since 2003. In Game 2 of the NL Division Series against the Atlanta Braves on October 8, Cain allowed one unearned run in innings but received a no-decision as the Giants lost 5–4 in 11 innings. In Game 3 of the NL Championship Series against the Philadelphia Phillies on October 19, he threw seven shutout innings and earned the win in a 3–0 victory over the Phillies. The Giants defeated the Phillies in six games. On October 28, Cain capped an impressive post-season performance as he pitched scoreless innings in Game 2 of the World Series against the Texas Rangers (a 9–0 Giants' victory) to become the fifth pitcher to pitch at least 20 innings in the postseason without allowing an earned run. His total post-season stats of a 2–0 record, with a 0.00 ERA through 21 innings pitched helped the Giants win their first championship in San Francisco.