By Erich Schwartzel and Joe Flint

LOS ANGELES -- The departure of Kevin Mayer -- just six months after overseeing the launch of Walt Disney Co.'s streaming service, Disney+ -- leaves a big hole at what has become a bright spot for a company widely hit by the pandemic.

While the rest of Disney, including its movie studio, ESPN sports empire and especially its theme parks, has been rocked by the coronavirus, Disney+ has flourished, picking up more than 54 million subscribers since it launched late last year.

Still, the streaming platform faces speed bumps. The shutdown of most television and movie production has hampered plans to increase its original content, and new rivals, including AT&T Inc.'s HBO Max and Comcast Corp.'s Peacock, are coming on the scene.

After more than two decades climbing the ranks at Disney, Mr. Mayer is leaving his role as head of direct-to-consumer and international operations to become chief executive of short-video app TikTok, owned by Chinese tech giant Bytedance Ltd. Disney tapped Rebecca Campbell, who has held several senior posts at the company and is one of its highest-ranking female executives, to succeed him.

Mr. Mayer was put in charge of Disney's streaming strategy after years of crafting the company's biggest deals. Being appointed to oversee the company's priority was seen as a vote of confidence in the executive, whom many considered a candidate for the CEO job that eventually went to Bob Chapek.

He has instead become the latest top-ranking lieutenant of Robert Iger, the company's longtime CEO-turned-executive chairman, to leave after a succession battle and as the company faces the challenges posed by the pandemic.

In an interview Monday, Mr. Mayer said he left not because he lost out on the CEO job, but that the TikTok role was too good to pass up. "The only reason I'm leaving is for what I think of as a once-in-a-lifetime opportunity," he said.

Several shows being produced by Disney's Marvel Studios for debuts this year and in 2021 have been delayed by the production shutdown. Disney has also pushed would-be theatrical releases to Disney+ in the coming months, including the children's book adaptation "Artemis Fowl" and a filmed version of the blockbuster musical "Hamilton."

Mr. Mayer said he wasn't concerned by new streaming competitors entering the fray. "The marketplace is a big growing pie," he said.

Mr. Mayer had little creative experience before taking on Disney+. Some shows the service ordered ended up being shifted to sister platform Hulu, including "High Fidelity," because they were deemed too adult. A reboot of the Disney Channel show "Lizzie McGuire" for Disney+ has also had creative issues, and its future is in limbo as Disney and show star Hilary Duff try to get on the same page, according to people familiar with the matter.

Since the pandemic forced all employees to work from home, Mr. Mayer has been managing the rollout of Disney+ in several new international markets. The success of those launches, he said, had persuaded him that the service could continue without him. "I am convinced that this team can replicate these launches and continue to grow the service in my absence," he said.

Mr. Mayer's portfolio at Disney includes more than just Disney+. He oversees other streaming efforts at Hulu and ESPN+, along with global advertising sales and international distribution for the Disney Channel and other networks.

Ms. Campbell, the new head of Disney+, rose through Disney's ABC television-stations division. She started as a programming executive and then general manager at WPVI-TV Philadelphia before running the flagship WABC-TV New York station and then the whole group.

She is charismatic and well liked within the company, people who have worked with her said, and is seen as a loyal soldier. She is also close to Mr. Iger, Disney insiders said.

In 2017, Ms. Campbell was named to a senior position with the corporate division that includes Disney+, heading operations in Europe, the Middle East and Africa. After being replaced last year in that role by an executive who came over in Disney's acquisition of Twentieth Century Fox film and TV studios, she was named president of Disneyland Resort.

Like Mr. Mayer, Ms. Campbell isn't seen as a creative executive, although ABC's daytime-programming division reported to her when she ran the station group. While she has limited experience in the streaming world, she has more operational experience than her predecessor did when he started at the service. A Disney spokeswoman said Ms. Campbell wasn't available to comment.

Mr. Mayer is joining TikTok as usage of the short-video app is surging, drawing scrutiny from some lawmakers worried about Chinese tech intrusions in the U.S. "This is a natural next step for me," Mr. Mayer said. "It's a new way for me to have one more go at it."

He isn't the first would-be Disney CEO to leave the company after getting passed over for the top job.

In early 2015, longtime Disney executive Tom Staggs was named chief operating officer of the company, beating out finance chief Jay Rasulo, who left the company in the following months. Mr. Staggs was widely seen as Mr. Iger's heir apparent, but in April 2016 he announced his departure after being told the Disney board wanted to broaden its search for the next CEO.

The next bake-off came in March 2018, when Mr. Iger reorganized the company and placed Mr. Mayer in charge of the direct-to-consumer and international divisions, which included the company's burgeoning streaming efforts. Mr. Chapek, another longtime Disney executive who was at the time in charge of parks, added consumer products to his portfolio.

Both were considered possible CEOs, but Mr. Mayer had been seen inside Disney and on Wall Street as the favorite, given his role in major Disney deals and his stewardship of the important streaming strategy.

--Shan Li contributed to this article.

Write to Erich Schwartzel at erich.schwartzel@wsj.com and Joe Flint at joe.flint@wsj.com