The 2005 National League Championship Series (NLCS), the second round of the 2005 National League playoffs, matched the Central Division champion and defending league champion St. Louis Cardinals against the wild card qualifier Houston Astros, a rematch of the 2004 NLCS. The Cardinals, by virtue of having the best record in the NL during the 2005 season, had the home-field advantage. The Astros won the series four games to two, and became the National League champions; they faced the American League champion Chicago White Sox in the 2005 World Series.

The Cardinals and Astros were victorious in the NL Division Series (NLDS), with the Cardinals defeating the West Division champion San Diego Padres three games to none, and the Astros defeating the East Division champion Atlanta Braves three games to one. St. Louis manager Tony La Russa, who won AL pennants with the Oakland Athletics in 1988–89–90 and the NL flag in 2004, fell short in his bid to become the first manager in history to win multiple pennants in both major leagues, although he did so in 2006 and again in 2011. The NLCS also closed with the last game ever played at St. Louis' Busch Stadium (II), which the Cardinals departed after 40 seasons.

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