Rose, 30, is seeking full custody of the couple's 19-month-old son, Sebastian, according to court papers, reported People magazine.
The couple got married on July 8, 2013.
Just two weeks ago, Rose honoured Khalifa on Instagram.
"Happy 27th Birthday. I'll love you forever... Hope this year is an amazing one for you sweetheart," she had captioned a photo of them holding each other tight.
She was also recently signed to Nick Cannon's management company, NCredible Entertainment, and has been spotted with the TV personality.