Frankel was part of the original Bravo network cast when the show premiered in 2008 and stayed on until 2010, leaving the series during the third season. She returned in 2015 during the seventh season.
"I have decided to leave the 'Housewives' franchise to explore my next chapter," Frankel said in a statement to Variety.
"It's time to move on and focus on my daughter, my philanthropy and my production partnership with Mark Burnett, producing and starring in shows which represent a shift in the conversation for women," she said.
"My experience at Bravo has been an incredibly magical ride. I am so grateful to them for highlighting my entrepreneurialism and allowing me to pave the way for many women to achieve their goals," Frankel added.
Frankel accepted a deal with MGM Television and Mark Burnett earlier this year to create unscripted projects, produce and possibly appear in them.