Kardashian, who with her California socialite sisters Kim and Kourtney rose to fame in "Keeping Up with the Kardashians," will appear on the U.S. version of the show from November.
She will share duties with Mario Lopez, host of syndicated entertainment news magazine show "Extra," Fox said in a statement.
"X Factor" creator Simon Cowell said in September that Kardashian, 28, was his top choice to co-host the singing contest following his firing in January of little-known British TV personality Steve Jones, who had the job as host for the show's first season in 2011.
"The worst kept secret in Hollywood is out," Cowell said in a statement on Tuesday.
"Mario and Khloe are our hosts. They will debut on our first live show in November and I couldn't be happier."
Kardashian married basketball player Lamar Odom in 2009, and the pair got their own spinoff show last year. She has more than 7 million followers on Twitter and has been in the news recently over the couple's efforts to have a baby.
Lopez, 39, is less well known but the former actor hosts "Extra" as well as a radio show "On with Mario Lopez." He is also an author of several fitness books.
Kardashian and Lopez complete the celebrity overhaul of "The X Factor" after a disappointing first season. Britney Spears and former Disney Channel star Demi Lovato made their debut as judges in September, replacing Paula Abdul and singer Nicole Scherzinger, who were also fired in January.
(Reporting By Jill Serjeant; editing by Todd Eastham)
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