Rancic will leave E! News as a day-to-day anchor from August 10 but will continue in her role on Fashion Police and as co-host of E!'s Live From the Red Carpet.
"For more than a decade, I was fortunate enough to play a role in the success of E! News and will miss my family at the show," she told E! News.
"At the same time, I am excited to not only continue as host of two major franchises on E! but also executive produce the aspirational new show Rich in Faith for Oxygen as well as take my wine and clothing lines to the next level."
It has been a difficult year for Rancic, who told People she and husband Bill Rancic learned in January that a surrogate had miscarried their last remaining embryo.
The following month the 40-year-old came under fire when during an Oscars Fashion Police segment she said Disney actress Zendaya's dreadlocked hairstyle smelt like patchouli oil or weed, which was understood by some to be racially insensitive.
Her comments sparked a stoush with Fashion Police regular Kelly Osbourne who then left the show.