Kramp-Karrenbauer, 56, won the leadership with 517 from 999 votes cast by delegates. Her rival, Friedrich Merz, won 482 votes in a run-off. A third candidate, Health Minister Jens Spahn, was eliminated in a first round of voting.
Kramp-Karrenbauer made her case ahead of the vote by saying the CDU had to maintain its position as the "last unicorn in Europe," the bloc's last successful catch-all party.
She also made a reference to her nickname, "mini Merkel," saying, "People consider me a 'mini,' a copy, a simple 'more of the same,' but I can tell you that I stand here as my own person, just as life has shaped me and of that I am proud."
The 56-year-old former state premier gained the nickname because of her pragmatic centrist political style and her reputation as a Merkel loyalist.
Kramp-Karrenbauer has been the CDU's general secretary, in charge of day-to-day political strategy, since February. She was previously a popular governor of western Saarland state.