In the negotiations to form a coalition government under Chancellor Angela Merkel following the 2009 federal elections, he was a member of the working group on economic affairs and energy, led by Annette Schavan and Andreas Pinkwart.

In the negotiations to form a fourth cabinet under Merkel following the 2017 federal elections, Kretschmer co-chaired the working group on transport and infrastructure, alongside Alexander Dobrindt and Sören Bartol.

In December 2021, ZDF journalists discovered a plot by anti-vaccine and anti-lockdown extremists to assassinate Kretschmer, which led to an investigation by Saxon police and searchings for weapons through several houses in Dresden.

[11][12] Since 2022, Kretschmer, alongside Karl-Josef Laumann, has been chairing a working group in charge of drafting policies on social security for the CDU's new party platform.

[12] During his tenure as secretary general of the CDU in Saxony, Kretschmer faced criticism after reports surfaced in 2010 that personal meetings with party chairman and Minister-President Stanislaw Tillich were offered to potential corporate sponsors in exchange for donations.