In 1992 Reiche was one of the founding members of the Ring Christlich-Demokratischer Studenten (Association of Christian-Democrat Students, RCDS) in Potsdam and in the same year she joined the Junge Union. Since 1996 she has also been member of the CDU. In 2000 Katherina Reiche became a member of the federal executive of the CDU and she also is part of the party's executive board in the state of Brandenburg.
Since 1998 she has been a member of the Bundestag. There she was chairman of the working group Bildung und Forschung ("Education and Science") in the years 2002 to 2005. In November 2005 she became deputy chairman of the CDU/CSU's parliamentary group in the sectors Bildung und Forschung ("Education and Science") and Umwelt, Naturschutz und Reaktorsicherheit ("Environment, Nature Conservation and Nuclear Safety").
During the election campaign in 2002 she was conscripted into the CDU/CSU's competence team by then chancellor candidate Edmund Stoiber, as an expert on women,youth and family policies.This decision was criticized by conservative circles inside the two parties,because Reiche was an unmarried mother at that point of time.
She is a political confidant of today's Federal Minister for Family Affairs, Senior Citizens, Women and Youth Ursula von der Leyen.
During the election campaign 2005 she denominated the opponents of genetic engineering as "Bioterroristen" ("Bioterrorists"). She also criticized the two then government parties SPD and the Greens for trying to catch votes with this subject and stiring up the people's fears for the future.