DeGeneres released a trailer on her Twitter account, and said Meghan would be appearing on The Ellen Show on Thursday.
The high-profile interview comes eight months after the former Suits star’s bombshell chat with Oprah Winfrey.
Meghan and the Duke of Sussex accused an unnamed member of the royal family of racism during their controversial talk with Winfrey.
They also said the institution of the monarchy failed to support the duchess when she had suicidal thoughts, and spoke of Harry’s strained relationships with the Prince of Wales and the Duke of Cambridge.
The show’s Ellentube.com website said: “The activist and co-founder of Archewell will chat with Ellen about growing up and returning to California, as well as her New York Times bestselling children’s book The Bench.”
In the trailer for The Ellen Show, the duchess, in a white blouse with cut-away detail on the sleeves, chatted about how she used to drive to the same Warner Brothers site for auditions.
Meghan added: “So to drive in today was very different.”
She said she would drive her “very, very old” Ford Explorer Sport and the key stopped working in the driver’s side door.
“I would open the trunk and climb in and then pull it shut behind me and crawl over all my seats to get out, that’s how I would come to and fro,” the duchess said
Asked by DeGeneres if anyone saw her, Meghan replied: “No, I would play it off. I go like, ‘Oh, I’m just looking for my resume and my highlighters or my script’.”
DeGeneres wrote on Twitter: “A lot has changed since the last time Meghan, The Duchess of Sussex, was on the Warner Brothers lot. Don’t miss the rest of our interview tomorrow.”
Comedian and actress DeGeneres announced in May that she was stepping down from her eponymous TV show after the 19th series.
She said the decision to end her show, which finishes in spring 2022, was not the result of allegations of a toxic workplace environment.
She apologised to staff in 2020 after an internal review by Warner Bros found “deficiencies related to the show’s day-to-day management”.
The review was launched following reports of a toxic work environment on the programme.
Meghan was accused of bullying in March, with The Times reporting that the duchess allegedly drove out two personal assistants and “humiliated” staff on several occasions, which she denies.
Buckingham Palace has tasked an external legal team to assist its human resources team in an investigation into the claims.
DeGeneres is a friend of Harry and Meghan’s and has called them “the cutest couple, so down to earth”.
She previously defended them when they faced criticism after taking a series of private jets.
“I mean I can’t tell you how sweet they are. But the most important thing is I got to hold Archie. I fed Archie. I held Archie,” she said after meeting the Sussexes’ son in 2019.