The Duke and Duchess of Sussex are to take over the day-to-day running of their Archewell Foundation after a senior aide resigned as president.
Prince Harry and Meghan Markle will take the "full lead" following the departure of Mandana Dayani, a spokesman said.
The announcement that Ms Dayani, 40, has quit comes after a trailer promoting the Sussexes' Netflix docuseries was released on Thursday.
She ran the day-to-day operations of the media and charitable enterprise, signing up less than 18 months ago.
Her role will not be replaced, a spokesman for the couple said, adding:
"Ms Dayani has been an integral part of Archewell, and we are grateful for her passion, commitment, and leadership."
Ms Dayani was brought in to "move the company and its projects forward" during the couple's parental leave after the birth of their daughter, Lilibet, in June 2021.
She has "continued to shape its vision and future successfully," the spokesman continued.
"Her transition was mutually planned, with intent for the Duke and Duchess to now take full lead of their company."
Ms Dayani is "fully supportive" of the Sussexes in their new leadership roles, the spokesman said, adding that they remain friends.
Harry and Meghan's Netflix series
The one-minute preview for Harry and Meghan's Netflix documentary series sees the duke say: "I had to do everything to protect my family."
The trailer features never-before-seen private photographs of the couple, who are heard being asked "Why did you want to make this documentary?"
Harry replies: "No one sees what's happening behind closed doors."
The preview ends with Meghan saying: "When the stakes are this high, doesn't it make more sense to hear our story from us?"
The trailer was released as Prince William and wife Kate embarked on a royal visit to Boston in their first overseas trip as Prince and Princess of Wales.
They were quickly left reeling from a racism row engulfing Buckingham Palace.
Prince William had to be told mid-flight about comments made by his godmother to domestic abuse charity founder, Ngozi Fulani.
A statement was issued saying there was "no place for racism in our society" before the couple had set foot on US soil.
But they got their moment to shine after announcing the five winners of the Earthshot Prize at a glittering "green" carpet event in the city in Massachusetts.
Each winner of the prestigious award, aimed at finding solutions to repair and regenerate the planet, scooped a £1m prize to scale up pioneering projects in a bid to secure a stable climate.
(c) Sky News 2022: Harry and Meghan take full control of Archewell Foundation as senior aide leaves